title string | abstract string | doi string | has_route int64 |
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Synthesis of HIV Protease Inhibitor ABT-378 (Lopinavir) | A large scale process for the synthesis of HIV protease inhibitor candidate ABT-378 has been developed which utilizes an intermediate common to the synthesis of ritonavir, Abbott's first generation compound. The synthesis relies on the sequential acylation of this intermediate which is carried through as a mixture of d... | 10.1021/op990202j | 1 |
Efficient Molar-Scale Synthesis of 1-Methyl-5-acylimidazole Triflic Acid Salts | A new process for the molar-scale preparation of 1-methyl-5-acylimidazole triflic acid salts was developed. The new process consists of: (i) regioselective 3 N -tritylation of 5-acylimidazole to give 3-trityl-5-acylimidazoles, (ii) 1 N -methylation of 3-trityl-5-acylimidazoles, and (iii) hydrolysis of the resulting qua... | 10.1021/op990201r | 0 |
The Preparation and Isolation of Chloramphenicol Palmitate in Toluene | The development of a process for the preparation of the antibiotic chloramphenicol palmitate that did not use methylene chloride and that fit into the production plant with improved yields and product quality is described. Addition of DMF as a co-solvent allowed the use of toluene for the reaction and the isolation. Th... | 10.1021/op990200z | 0 |
Discovery and Development of a Commercial Synthesis of Azafenidin | A commercial synthesis of the DuPont herbicide azafenidin is described. Discovery of a novel synthesis of the triazolinone ring system and a practical, environmentally benign process to 5-cyanovaleramide were critical breakthroughs in enabling azafenidin to be manufactured at an acceptable cost. The process began with ... | 10.1021/op9901994 | 1 |
A Facile, One-Pot Procedure for the Preparation of 2-Phenyl-1,3-propanediol Monocarbamate, a Metabolite of Felbamate | A simple, one-pot procedure for the preparation of 2-phenyl-1,3-propanediol monocarbamate (MCF) has been developed. This procedure represents the most efficient method for preparing MCF published to date, and it is amenable to the large-scale laboratory production of this biologically relevant metabolite of felbamate. | 10.1021/op990198b | 0 |
The Development of a Manufacturable Synthesis of LY213829 | The development of a manufacturable synthesis of LY213829 (4-thiazolidinone-5-[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl] methyl) is described. Rather than reduction to eliminate the thiocarbonyl from the rhodanine moiety, the new route utilizes a novel concurrent ring opening with ammonia and re-cyclization with form... | 10.1021/op990197j | 1 |
A Concise Asymmetric Synthesis of A β-Lactam-Based Cholesterol Absorption Inhibitor | A concise, four-step, asymmetric synthesis of a β-lactam-based cholesterol absorption inhibitor, Sch 57939, was developed. The discovery of a one-step enantio- and diastereoselective synthesis of a trans -β-lactam provided easy access to the desired three chiral centers. A novel zinc phenoxide-promoted ether synthesis ... | 10.1021/op990196r | 1 |
Use of Sodium Bromate for Aromatic Bromination: Research and Development | Sodium bromate is a powerful brominating agent for aromatic compounds that contain deactivating substituents. A bromination process, in which sodium bromate was utilized, was optimized on laboratory scale. Addition of a strong acid into a stirred aqueous solution, or slurry, of the substrate and bromate salt at 40−100°... | 10.1021/op9901947 | 1 |
Efficient Synthesis of the Anticancer Drug Etoposide 4‘-Phosphate: Use of Benzylic Ether-Protecting Groups on the Carbohydrate Segment<sup>1</sup> | The prodrug etoposide phosphate 2 is synthesized efficiently in three steps in 54.6% overall yield from 4‘-demethylepipodophyllotoxin 3 . The strategy pursued in the synthesis of 2 places the phosphate on 3 prior to coupling with the sugar and employs benzyl ether-protecting groups on both the phosphate and the sugar, ... | 10.1021/op990193e | 1 |
Synthesis of a Spiro[cyclohex-1,1‘-isobenzofuranyl] Dopamine Receptor Antagonist | Two syntheses of the novel CNS agent, 2-fluoro-4-( trans )-(4-(3‘H-spiro[cyclohex-1,1‘-isobenzofuran]-4-yl)-piperazin-1-yl)-benzonitrile, 1, are presented. The first relied on a reductive alkylation with low regioselectivity (1:1) but was sufficient for the preparation of kilogram quantities. The second used a selectiv... | 10.1021/op990191u | 1 |
Process Development of (2-Nitrophenylcarbamoyl)-(<i>S</i>)-prolyl-(<i>S</i>)-3- (2-naphthyl)alanyl-<i>N</i>-benzyl-<i>N</i>-methylamide (SDZ NKT343) | (2-Nitrophenylcarbamoyl)-( S )-prolyl-( S )-3-(2-naphthyl)alanyl- N -benzyl- N -methylamide ( 1; SDZ NKT343) is a human NK-1 tachykinin receptor antagonist. The development of a robust process for a multikilogram scale, chromatography-free preparation of this compound is described. The new four-step synthesis was based... | 10.1021/op990188a | 1 |
A Cost-Efficient Synthesis of Simvastatin via High-Conversion Methylation of an Alkoxide Ester Enolate | A cost-efficient synthesis of simvastatin ( 2 ), starting from mevinolin (lovastatin) ( 1a ) or its precursor mevinolinic acid ( 1b ), is reported. This synthesis involves the use of a new intermediate, lovastatin cyclopropylamide ( 3 ), eliminating two chemical steps of protection and deprotection of the open dihydrox... | 10.1021/op990187i | 1 |
Dilevalol via Resin-Mediated Epimerization: A Case Study. Reaction Mechanism to Reactor Design to a Viable Process | A case study on a novel commercial process for the preparation of dilevalol, 5-[1-hydroxy-2-[(1-methyl-3-phenylpropyl)-amino]ethyl]salicylamide, ( R, R )- 1, from crude ( S, R )- 1, is described. This covers all of the work from the initial laboratory observation of an acid-induced racemization of the benzylic carbinol... | 10.1021/op990185y | 1 |
Large-Scale Synthesis of Antisense Oligonucleotides without Chlorinated Solvents | It is demonstrated that mixed-sequence phosphorothioate oligodeoxyribonucleotides can be synthesized on scales from 1 μmol up to 80 mmol without using chlorinated solvents such as dichloromethane or dichloroethane, while preserving both high yield and purity of the product. A solution of dichloroacetic acid in organic ... | 10.1021/op990183d | 0 |
Process Research for the Synthesis of RWJ-51204, A Novel Anxiolytic Agent | RWJ-51204, the lead compound in our pyrido [1,2- a ] benzimidazole (PBI) series, was shown to exhibit anxiolytic efficacy in animal models at doses which did not cause central nervous system side effects commonly observed with other anxiolytic agents. To prepare supplies of drug substance for early toxicological and cl... | 10.1021/op990182l | 1 |
Preparation of Grignard Reagents: FTIR and Calorimetric Investigation for Safe Scale-Up | Preparation of Grignard reagents from organic halides and magnesium pose potential safety hazards on scale-up due to their high exothermic potential which can lead to overpressurization, discharge of contents, or explosion. One of the main challenges arises in ensuring the reaction has initiated before excessive accumu... | 10.1021/op9901801 | 0 |
A Large, Laboratory-Scale Synthesis of [4-(2-(2<i>H</i>)-Tetrahydropyranyloxy)phenyl]boronic Acid | A large, laboratory-scale synthesis of a useful intermediate for coupling reactions, [4-(2-(2 H )-tetrahydropyranyloxy)phenyl]boronic acid, is described. | 10.1021/op990107a | 0 |
Shedding Some Light on Crystallization Issues: Lecture Transcript from the First International Symposium on Aspects of Polymorphism and Crystallization − Chemical Development Issues<sup>1</sup> | ADVERTISEMENT RETURN TO ISSUEPREVSummary of Lecture T...Summary of Lecture TranscriptNEXTShedding Some Light on Crystallization Issues: Lecture Transcript from the First International Symposium on Aspects of Polymorphism and Crystallization − Chemical Development Issues1Norman LewisView Author Information Synthetic Che... | 10.1021/op990104y | 1 |
A Practical and Efficient Synthesis of <i>p</i>-Menthane-3,8-diols | The diastereomeric repellents of p -menthane-3,8-diol were produced from citronellal by treatment with 0.25% sulfuric acid at 50 °C for 11 h to give 97.9% conversion and 92.3% selectivity and citronellal acetal by-products with only 2.7%. The crude products were crystallized from n -heptane at −50 °C for 20 h to give p... | 10.1021/op9901036 | 0 |
Efficient Large Scale Synthesis of 2‘-<i>O</i>-Alkyl Pyrimidine Ribonucleosides | An efficient process to synthesize 2‘- O -alkyl pyrimidine ribonucleosides in high yield has been described. The inexpensive method was used on a multikilogram-scale synthesis and optimized reaction conditions have been investigated. | 10.1021/op990100t | 0 |
Synthesis and Scale-Up of 2,4,6,8,10,12-Hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane from 2,6,8,12-Tetraacetyl-4,10-dibenzyl-2,4,6,8,10,12-hexaazaisowurtzitane (HNIW, CL-20) | A two-stage conversion of 2,6,8,12-tetraacetyl-4,10-dibenzyl-2,4,6,8,10,12-hexaazaisowurtzitane to 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane, involving nitrosation followed by nitration, is described. It is shown that the purity of the final product obtained by this method is superior to that obtained ... | 10.1021/op990097d | 0 |
A Liquid-Phase Process Suitable for Large-Scale Synthesis of Phosphorothioate Oligonucleotides | A new process for the preparation of large amounts of thioate oligonucleotides in a quasi-classical solution condition is described. This method takes advantage of the use of poly(ethylene glycol) as a soluble, inert support during the synthesis. The quality and amount of the desired oligonucleotides are improved by th... | 10.1021/op990096l | 0 |
The Dimethoxytrityl Resin Product Anchored Sequential Synthesis Method (DMT PASS): A Conceptually Novel Approach to Oligonucleotide Synthesis | Presented is a conceptually novel approach to oligonucleotide synthesis referred to herein as dimethoxytrityl resin product anchored sequential synthesis (DMT PASS). The DMT PASS process is characterized by the reaction of a 3‘-protected nucleoside or oligonucleotide with an excess of a nucleotide 3‘-phosphoramite or H... | 10.1021/op990095t | 0 |
Development of a Catalytic Tributyltin Hydride Cyclisation Process | The development of a pilot plant process to prepare the spirocyclic piperidine ( 2 ) from the tetrahydropyridine ( 4 ) via a radical cyclisation reaction is described. The pilot plant process involves the use of a catalytic amount of tributyltin hydride (0.14 equiv) generated in situ by the reaction of tributyltin chlo... | 10.1021/op9900941 | 0 |
New Synthesis of a Protected Ketonucleoside by a Non-Cryogenic Oxidation with TFAA/DMSO<sup>1</sup> | An improved synthesis of the ketonucleoside 2‘-Oxo-3‘,5‘- O -[1,1,3,3-tetrakis(1-methylethyl)-1,3-disiloxanediyl]-cytidine ( 6 ), an intermediate in the synthesis of the potent anti-tumor agent 1 (MDL 101,731 or FMdC), is reported which incorporates a trifluoroacetic acid/dimethylsulfoxide oxidation process. This oxida... | 10.1021/op9900939 | 1 |
Large-Scale Synthesis of Oligonucleotide Phosphorothioates Using 3-Amino-1,2,4-dithiazole-5-thione as an Efficient Sulfur-Transfer Reagent | A commercially available and inexpensive compound, 3-amino-1,2,4-dithiazole-5-thione (ADTT), is discovered to be a new sulfur-transfer reagent for solid-phase synthesis of oligonucleotide phosphorothioates via the phosphoramidite method. The efficiency of ADTT was investigated by solid-phase syntheses of dinucleotide a... | 10.1021/op990092g | 0 |
Process Development for Purification of Therapeutic Antisense Oligonucleotides by Anion-Exchange Chromatography | This article describes the development of an anion-exchange chromatography method for purification of phosphorothioate antisense oligonucleotides. A variety of operating conditions were studied and optimized at small scale. These optimized parameters were used to generate data at multigram scale. The selected method ca... | 10.1021/op990091o | 0 |
Clay-Supported Liquid−Liquid−Solid Phase Transfer Catalysis: Synthesis of Benzoic Anhydride | Solid-supported phase transfer catalysed reactions typically involve polystyrene supports cross-linked with divinyl benzene. The use of commercially available clay as a support for the PTC reaction is attractive. This paper reports the preparation of benzoic anhydride from benzoyl chloride and sodium benzoate using cla... | 10.1021/op990087c | 0 |
Improved Process for the Preparation of Nucleosidic Phosphoramidites Using a Safer and Cheaper Activator | A new, simplified commercial process for the preparation of nucleosidic phosphoramidites, key raw materials for the automated solid-supported synthesis of oligonucleotide-based drugs, was developed. Phosphitylation of a variety of protected nucleosidic derivatives ( 1 − 4 ) with a small excess of 2-cyanoethyl- N, N, N ... | 10.1021/op990086k | 0 |
Development Summary towards a Manufacturable Process for R 83842 [(<i>S</i>)-6-[(4-chlorophenyl) (1H-1,2,4-triazol-1-yl)methyl]-1-methyl-1H-benzotriazole] | A scalable process to produce enantiomeric R 83842, ( S )-6-[(4-chlorophenyl) (1 H -1,2,4-triazol-1-yl)methyl]-1-methyl-1 H -benzotriazole, is developed and described as a lecture* transcript. Cheap and safe reagents have been used. A typical procedure for oxidative destruction of aqueous cyanide waste, and stability d... | 10.1021/op990081n | 1 |
On-Line Monitoring of Process HPLC by Sensors | On-line process control with a SAW (surface acoustic wave) sensor-based gas-sensor microsystem (SAGAS PC = surface acoustic wave based aroma and gas analyzing system) for industrial applications is presented. The monitoring of the gradient former of a preparative HPLC system is a useful tool for the on-line process con... | 10.1021/op990080v | 0 |
Process Research and Development of <scp>l</scp>-Alanyl-<scp>l</scp>-glutamine, a Component of Parenteral Nutrition | A large-scale manufacturing method of l -alanyl- l -glutamine used for a component of parenteral nutrition has been studied. The method consisted of a reaction of d -2-chloro- or d -2-bromopropionic acid with thionyl chloride and Schotten−Baumann reaction with l -glutamine followed by ammonolysis reaction. The intermed... | 10.1021/op990079w | 1 |
Synthesis of Antisense Oligonucleotides: Replacement of 3H-1,2-Benzodithiol-3-one 1,1-Dioxide (Beaucage Reagent) with Phenylacetyl Disulfide (PADS) As Efficient Sulfurization Reagent: From Bench to Bulk Manufacture of Active Pharmaceutical Ingredient | It is demonstrated that phosphorothioate oligodeoxyribonucleotides can be synthesized on scales from 1 μmol to 150 mmol using phenylacetyl disulfide (PADS) as an efficient and economical replacement for Beaucage reagent. A 0.2 M solution of PADS in a mixture of 3-picoline and acetonitrile (1:1 v/v) as solvent with 60−1... | 10.1021/op990077b | 0 |
Process Chemistry in the Pharmaceutical Industry Edited by Kumar G. Gadamasetti. Marcel Dekker: New York, Basel. 1999. 473 pp. $195.00. ISBN 0-8247-1981-6 | ADVERTISEMENT RETURN TO ISSUEPREVBook ReviewNEXTProcess Chemistry in the Pharmaceutical Industry Edited by Kumar G. Gadamasetti. Marcel Dekker: New York, Basel. 1999. 473 pp. $195.00. ISBN 0-8247-1981-6Derek RobinsonView Author Information Little Mill, Pontypool, Gwent, U.K. Cite this: Org. Proc. Res. Dev. 1999, 3, 6, ... | 10.1021/op990075r | 0 |
The Chemical Development of the Commercial Route to Sildenafil: A Case History | This paper is a case history of the chemical development of sildenafil which covers various aspects of work in chemical development namely: route selection, scale-up issues, the development of an efficient synthesis with high throughput, process safety, and environmental issues. Interesting chemical points include impr... | 10.1021/op9900683 | 1 |
New Practical Synthesis of Tenidap | The development of a new, practical synthesis to tenidap is described. N, O -Dialkoxy(aryloxy)carbonylation of 5-chloro-2-oxo-2,3-dihydroindole, followed by removal of the O- alkoxy(aryloxy)carbonyl group gave 1-[alkoxy(aryloxy)carbonyl]-5-chloro-2-oxo-2,3-dihydroindoles in good yields. The latter compounds were thenoy... | 10.1021/op990067a | 1 |
Process Improvements in the Production of a Novel Non-Xanthine Adenosine A<sub>1</sub> Receptor Antagonist. A “One-Pot” Horner-Emmons Isomerization Reaction | Pilot plant scale synthesis of 2-[3-(2-phenylpyrazolo[1,5- a ]pyridin-3-yl-1(6 H )-pyridazin-6-one)-1-cyclohexen-1-yl] acetic acid (FR166124) is described. The process involved efficient isomerization of regioisomers produced in a Horner-Emmons reaction and employed ester exchange and hydrolysis with NaOH in MeOH. Chal... | 10.1021/op990066i | 1 |
Analysis, Synthesis and Design of Chemical Processes by R. Turton, R. C. Bailie, W. B. Whiting, and J. A. Shaeiwitz. Prentice Hall: New Jersey, 1999. 814 pp. ISBN 0-13-570565-70. £66. | ADVERTISEMENT RETURN TO ISSUEPREVBook ReviewAnalysis, Synthesis and Design of Chemical Processes by R. Turton, R. C. Bailie, W. B. Whiting, and J. A. Shaeiwitz. Prentice Hall: New Jersey, 1999. 814 pp. ISBN 0-13-570565-70. £66.Cite this: Org. Proc. Res. Dev. 1999, 3, 6, 494Publication Date (Web):August 3, 1999Publicati... | 10.1021/op990061l | 0 |
A Practical Synthesis of Phenylpropargyl Aldehyde from Phenylacetylene and <i>N</i>-Formylmorpholine | A synthesis of phenylpropargyl aldehyde is described employing formylation of a phenylacetylenic Grignard reagent with N -formylmorpholine. This method afforded the product in excellent yield. | 10.1021/op9900582 | 1 |
Phosphorus Ylides; Chemistry and Application in Organic Synthesis by Oleg I Kolodiazhnyi. Wiley-VCH: Weinheim, 1999. 555 pp. ISBN 3-527-29531-3. DM 248. | null | 10.1021/op990057+ | 0 |
Chlorobenzyl Alcohols from Chlorobenzyl Chlorides via Corresponding Benzoate Esters: Process Development Aspects | Kinetic studies in conversion of benzyl chlorides to corresponding alcohols via the benzoates are presented in this paper. The esterification reaction of 2-chlorobenzyl chloride, 4-chlorobenzyl chloride, 2,4-dichlorobenzyl chloride and benzyl chloride with aqueous sodium benzoate in the presence of phase transfer catal... | 10.1021/op9900535 | 0 |
Practical Chemo-Enzymatic Process for the Preparation of (1<i>R</i>,<i>cis</i>)-2-(2,2-Dihaloethenyl)-3,3-dimethylcyclopropane Carboxylic Acids | A practical chemo-enzymatic process for the preparation of optically active (1 R, cis )-2-(2,2-dichloro (or dibromo)ethenyl)-3,3-dimethylcyclopropane carboxylic acids (permethrinic or deltamethrinic acids) from racemic 1,1,1-trichloro-2-acetoxy-4-methyl-3-pentene is described. The key intermediate, enantiopure ( R )-1,... | 10.1021/op990052c | 1 |
Continuous and Batch Organomagnesium Synthesis of Ethyl-Substituted Silanes from Ethylchloride, Tetraethoxysilane, and Organotrichlorosilane for Production of Polyethylsiloxane Liquids. 1. Batch One-Step Synthesis of Ethylethoxysilanes and Ethylchlorosilanes | Development of batch one-step manufacturing process for ethylethoxy- and ethylchlorosilanes is desribed. The methodology of synthesis of ethyl-substituted silanes has been improved. The important factors for the successful synthesis have been determined. Among them are the replacement of the part tetraethoxysilane 3 by... | 10.1021/op990049t | 0 |
Hydrolases in Organic Synthesis. by U. T. Bornscheuer and R. J. Kaslauskas. Wiley-VCH: Weinheim, 1999. 336 pp. ISBN 3-527-30104-6. | ADVERTISEMENT RETURN TO ISSUEPREVBook ReviewNEXTHydrolases in Organic Synthesis. by U. T. Bornscheuer and R. J. Kaslauskas. Wiley-VCH: Weinheim, 1999. 336 pp. ISBN 3-527-30104-6.Nicholas J. TurnerView Author Information University of EdinburghCite this: Org. Proc. Res. Dev. 1999, 3, 6, 494Publication Date (Web):Septemb... | 10.1021/op9900481 | 0 |
Process Development of a Novel Non-Xanthine Adenosine A<sub>1</sub> Receptor Antagonist | (+)−( R )-1-[( E )-3-(2-phenylpyrazolo[1,5- a ]pyridin-3-yl)acryloyl]-2-piperidine ethanol (FK453) is a novel, potent adenosine A 1 receptor antagonist for the regulation of renal function. The development of a reliable process suitable for large scale manufacture is described. A Horner−Emmons reaction and a 1,3-dipola... | 10.1021/op990044w | 1 |
Synthesis of <i>p</i>-Aminophenol by Catalytic Hydrogenation of Nitrobenzene | The present work describes the preparation of p- aminophenol via single-step catalytic hydrogenation of nitrobenzene in acid medium. A conventional method of synthesis of p- aminophenol is a two-step reaction involving iron−acid reduction of p -nitrophenol. This method causes serious effluent disposal problems due to t... | 10.1021/op990040r | 0 |
Pyridinium Trifluoroacetate/<i>N</i>-Methylimidazole as an Efficient Activator for Oligonucleotide Synthesis via the Phosphoramidite Method | A new activator is reported for coupling phosphoramidites to a free 5‘-hydroxyl group during oligonucleotide synthesis. Pyridinium trifluoroacetate/ N -methyl imidazole is a remarkably efficient replacement for 1 H -tetrazole in the solid-supported synthesis of oligonucleotides. This reagent is safe and inexpensive, is... | 10.1021/op9900378 | 0 |
Practical Large-Scale Synthesis of Endothelin Receptor Antagonist S-0139 | Semisynthetic endothelin receptor antagonist S-0139 was synthesized in 14 steps from oleanolic acid 2 in a 20% overall yield on a multi-kilogram scale. Our previous synthesis of the oleanane skeleton was modified and improved to give phosphonate 9 as a key intermediate. The side chain on the 27-position was introduced ... | 10.1021/op990036f | 0 |
Tartaric and Malic Acids in Synthesis: A Source Book of Building Blocks, Ligands, Auxiliaries, and Resolving Agents By Jacek Gawronski and Krystyna Gawronska. Wiley Interscience: New York, 1999. 591 pp. ISBN 0471244511. £96.50. | ADVERTISEMENT RETURN TO ISSUEPREVBook ReviewNEXTTartaric and Malic Acids in Synthesis: A Source Book of Building Blocks, Ligands, Auxiliaries, and Resolving Agents By Jacek Gawronski and Krystyna Gawronska. Wiley Interscience: New York, 1999. 591 pp. ISBN 0471244511. £96.50.Martin FoxView Author Information Chirotech T... | 10.1021/op990034v | 0 |
Development of the Process of <i>p</i>-Nitroacetophenone and Benzoic Acid Manufacture by the Liquid-Phase Oxidation of Aromatic Compounds | The kinetic model of the ethyl benzene oxidation was applied to the design of the large-scale reactors of p -nitroacetophenone (chloramphenicol key intermediate) synthesis by p -nitroethyl benzene oxidation and benzoic acid synthesis by acetophenone oxidation. The factors allowing simplification of the above model are ... | 10.1021/op990030q | 0 |
Synthesis of <i>m</i>-Phenoxybenzaldehyde Starting from Chlorobenzene and <i>m</i>-Cresol: Some Aspects of Process Development | m -Phenoxybenzaldehyde (MPB) is an important intermediate for synthetic pyrethroids. In the present paper, an economic process scheme was developed to synthesize MPB starting from cheaper reactants. The process scheme was started with the synthesis of m -phenoxytoluene (MPT). Oxidation of MPT by air gave MPB, but the s... | 10.1021/op990028z | 1 |
Studies in Selectivity Aspects in the Synthesis of Aliphatic α-Bromoaldehydes | A highly selective process scheme was developed to synthesize α-bromoaldehydes by regulating the important process parameters from a reaction-engineering point of view. Thus, α-bromobutyraldehyde and α-bromoheptaldehyde were synthesized in very high selectivity starting with butyraldehyde and heptaldehyde. In the bromi... | 10.1021/op990025m | 0 |
Breaking the New Bottleneck: Automated Synthesis in Chemical Process Research and Development | An overview of the current methods, available systems, and applications of laboratory automation in chemical process research and development is given. Examples of the successful implementation of automated synthesis into reaction optimisation and process development are discussed. | 10.1021/op990020p | 0 |
Development of a Pilot Scale Process for the Anti-Alzheimer Drug (−)-Galanthamine Using Large-Scale Phenolic Oxidative Coupling and Crystallisation-Induced Chiral Conversion | (−)-Galanthamine has been synthesised using an efficient nine-step procedure, which in large scale affords 12.4 (6.7−19.1)% overall yield. The process improvements and optimization of each step are described. Notable steps include (i) an oxidative phenol coupling and (ii) crystallisation-induced chiral conversion of (±... | 10.1021/op990019q | 1 |
Kinetics and Process Parameter Studies in Catalytic Air Oxidation of Veratraldehyde to Veratric Acid | Kinetics and different process parameters for the air oxidation of veratraldehyde to veratric acid were studied. At a temperature of 130 °C, air pressure of 1 MPa, cobalt acetate loading of 0.03 mol/L, and an initial concentration of 30% w/v of veratraldehyde, the reaction was found to be first order with respect to ve... | 10.1021/op990018y | 0 |
Industrial Synthesis of the Key Precursor in the Synthesis of the Anti-Influenza Drug Oseltamivir Phosphate (Ro 64-0796/002, GS-4104-02): Ethyl (3<i>R</i>,4<i>S</i>,5<i>S</i>)-4,5-epoxy-3-(1-ethyl-propoxy)-cyclohex-1-ene-1-carboxylate | Starting from (−)-quinic acid, the title compound was synthesized in seven chemical steps and an overall yield of 35−38%. The route of the improved Gilead synthesis was not changed. However, significant improvements in each step led to a doubled overall yield, a 30% reduction in the number of unit operations, and an ex... | 10.1021/op9900176 | 1 |
A Practical Approach to Accelerated Process Screening and Optimisation | The development and operation of an automated workstation for performing solution-phase organic synthesis and on-line HPLC analysis is described. A wide scope of applications and chemistries, typically encountered in process development laboratories, are reported. The application of this workstation to process screenin... | 10.1021/op990016d | 0 |
Modern Catalytic Methods for Organic Synthesis with Diazo Compounds (From Cyclopropanes to Ylides) By M. P. Doyle, M. A. McKervey, and T. Ye. Wiley-Interscience: New York. 1998. 652 pp. ISBN 0-47113556-9. £100. | ADVERTISEMENT RETURN TO ISSUEPREVBook ReviewModern Catalytic Methods for Organic Synthesis with Diazo Compounds (From Cyclopropanes to Ylides) By M. P. Doyle, M. A. McKervey, and T. Ye. Wiley-Interscience: New York. 1998. 652 pp. ISBN 0-47113556-9. £100.Cite this: Org. Proc. Res. Dev. 1999, 3, 3, 235–236Publication Dat... | 10.1021/op990015l | 0 |
Azolides in Organic Synthesis and Biochemistry By H. A. Staab, H. Bauer, and K. M. Schneider. Wiley-VCH: Weinheim, 1998. 502 pp. ISBN3-527-29314-0. £95.00. | ADVERTISEMENT RETURN TO ISSUEPREVBook ReviewNEXTAzolides in Organic Synthesis and Biochemistry By H. A. Staab, H. Bauer, and K. M. Schneider. Wiley-VCH: Weinheim, 1998. 502 pp. ISBN3-527-29314-0. £95.00.Cite this: Org. Proc. Res. Dev. 1999, 3, 3, 235Publication Date (Web):March 27, 1999Publication History Published onl... | 10.1021/op9900131 | 0 |
Continuous Single-Stage Organomagnesium Synthesis of a Mixture of Ethylethoxysilanes and Dimethylethylethoxysilane | Simultaneous synthesis of ethylethoxysilanes and dimethylethylethoxysilane from a mixture of ethyl chloride, tetraethoxysilane, and dimethyldichlorosilane with magnesium (supply rate 75−100 g h - 1 ) was studied. Schemes of intermediate processes are proposed. Reactivity of dimethyldichlorosilane and diethyldichlorosil... | 10.1021/op990011g | 0 |
Production of (<i>R</i>)-Aminoglutethimide: A New Route from 1-Chloro-4-nitrobenzene | The development of a short, safe and enantioselective route for the preparation of ( R )-aminoglutethimide is described. The process was designed for economic large-scale manufacture of the bulk drug substance to acceptable quality standards, to allow clinical evaluation of the single enantiomer over the existing racem... | 10.1021/op9900075 | 1 |
A Convenient Practical Method for the Preparation of (−)-(1<i>S</i>,2<i>S</i>)-5-Norbornene-2-carboxylic Acid, Incorporating Efficient Recovery of the Chiral Auxiliary <scp>d</scp>-Pantolactone | A convenient practical method was developed for the preparation of enantiomerically pure (−)-(1 S,2 S )-5-norbornene-2-carboxylic acid, wherein the chiral auxiliary d -pantolactone was recovered efficiently. | 10.1021/op990006c | 0 |
A Versatile and Cost-Effective Approach to Automated Laboratory Organic Synthesis | The application of a commercial laboratory automated synthesis system, the Anachem SK233 Workstation, is described for use in organic synthesis. A novel reactor design feature has been developed to enable the sampling of reactions under ambient to reflux temperatures while maintaining an effective inert atmosphere. Up ... | 10.1021/op990005k | 0 |
A Practical Asymmetric Synthesis of the Antiviral Agent Lobucavir, BMS-180194. | ADVERTISEMENT RETURN TO ISSUEPREVAddition/CorrectionNEXTORIGINAL ARTICLEThis notice is a correctionA Practical Asymmetric Synthesis of the Antiviral Agent Lobucavir, BMS-180194.Janak Singh, Gregory S. Bisacchi, Saleem Ahmad, Jollie D. Godfrey, Thomas P. Kissick, Toomas Mitt, Octavian Kocy, Truc Vu, Chris G. Papaioannou... | 10.1021/op990004s | 0 |
Fine Chemicals from Lignosulfonates. 2. Synthesis of Veratric Acid from Acetovanillon | An optimisation study based upon experimental data obtained from multivariate statistical experimental design and modelling for the haloform reaction used for synthesis of 3,4-dimethoxybenzoic acid from 3,4-dimethoxy acetophenone is reported. It is shown how the different controllable process variables influence both t... | 10.1021/op9900030 | 1 |
Fine Chemicals from Lignosulfonates. 1. Synthesis of Vanillin by Oxidation of Lignosulfonates | The oxidation of lignosulfonates (LS) to vanillin by persulphate, oxygen, and a variety of catalytic systems has been investigated. Cobalt and copper catalysts appeared to be the most effective in the oxidation by oxygen. An investigation where multivariate mathematical and statistical design and modelling have been us... | 10.1021/op9900028 | 0 |
A Practical Synthesis of Multitargeted Antifolate LY231514 | A concise and scalable synthesis of LY231514 ( 1 ), a new pyrrolo[2,3- d ]pyrimidine-based antitumor agent, is presented. Reaction of 2-bromo-4-arylbutanal 9 with 2,4-diamino-6-hydroxypyrimidine ( 10 ) regioselectively provided pyrrolo[2,3- d ]pyrimidine 11, representing the core structure of the drug, in good yield. A... | 10.1021/op9802172 | 1 |
Application of Modified Flavone Closure for the Preparation of Racemic L86-8275 | The laboratory preparation of racemic L86-8275 ( 1a ) and the salt ( 1b ) is described in 7% overall yield. Our method eliminated a number of chromatography steps from the patent procedure and improved the flavone-forming reaction by employing a stepwise mechanism. Solvent-free conditions for the demethylation step are... | 10.1021/op980215h | 1 |
Synthesis of ABT-378, an HIV Protease Inhibitor Candidate: Avoiding the Use of Carbodiimides in a Difficult Peptide Coupling | An alternative to carbodiimide-mediated peptide coupling protocols has been developed for a carboxylic acid prone to decomposition by polymerization. This method, involving the in situ generation of an acyl imidazolide, has been applied to the preparation of a lead clinical HIV protease inhibitor candidate, ABT-378. Th... | 10.1021/op980214p | 0 |
Enantioselective Synthesis of Brinzolamide (AL-4862), a New Topical Carbonic Anhydrase Inhibitor. The “DCAT Route” to Thiophenesulfonamides | A large scale synthesis of the topical carbonic anhydrase inhibitors AL-4623A ( 13a ·HCl) and AL-4862 ( 13b ) from 3-acetyl-2,5-dichlorothiophene (“DCAT”, 1 ) is described. Reaction of 1 with NaSBn gave thioether 2, which was converted via sulfenyl chloride 3 and sulfenamide 5 to sulfonamide 6 . Bromination of 6 gave b... | 10.1021/op9802125 | 1 |
Scale Up of a Ritter Reaction | The Ritter reaction of secondary or tertiary alcohols with acrylonitrile provides easy access to acrylamides which would otherwise be difficult to prepare. A safe procedure for conducting this reaction is described. | 10.1021/op980211c | 0 |
New Disulfide Route to 3-(1-Piperazinyl)-1,2-benzisothiazole. Nucleus for Atypical Antipsychotic Drugs | A new, one-step commercial process for the preparation of 3-(1-piperazinyl)-1,2-benzisothiazole hydrochloride, a key intermediate for the syntheses of some new, “atypical antipsychotic” drugs, was developed. Reaction of bis(2-cyanophenyl) disulfide with excess piperazine at 120−140 °C for 3−24 h in the presence of smal... | 10.1021/op980210k | 1 |
Synthesis of CMI-977, a Potent 5-Lipoxygenase Inhibitor | CMI-977 is a potent 5-lipoxygenase inhibitor that intervenes in the production of leukotrienes and is presently being developed for the treatment of chronic asthma. It is a single enantiomer with an all - trans (2 S,5 S ) configuration. Of the four isomers of CMI-977, the S, S isomer was found to have the best biologic... | 10.1021/op980209l | 1 |
Synthesis of (<i>R</i>)-(−)-1-Piperidino-3,3-dimethylbutan-2-ol: Application in the Molar Scale Asymmetric Ethylation of <i>trans</i>-Crotonaldehyde | A simple three-step preparation of ( R )-(−)-1-piperidino-3,3-dimethylbutan-2-ol (amino alcohol catalyst for the Noyori asymmetric alkylation of aldehydes) based on a classical resolution of the racemate is described. Use of this catalyst in a detailed study of the asymmetric ethylation of trans -crotonaldehyde produci... | 10.1021/op980208t | 0 |
Reduction of an Enaminone: Synthesis of the Diamino Alcohol Core of Ritonavir | The reduction of (5 S )-2-amino-5-dibenzylamino-4-oxo-1,6-diphenylhex-2-ene was optimized for diastereoselectivity and overall conversion to (2 S,3 S,5 S )-5-amino-2-dibenzylamino-3-hydroxy-1,6-diphenylhexane ( 2a ). A two-step reduction sequence is described wherein the enamine is reduced with a borane-sulfonate deriv... | 10.1021/op9802071 | 1 |
A Practical Synthesis of Cycloheptane-1,3-dione | A three-step synthesis of cycloheptane-1,3-dione has been developed which avoids the use of heavy metal or explosive reagents and provides access to multigram quantities of this material. | 10.1021/op9802069 | 1 |
Preparation of Carboxamides via Carboxylic−Phosphoric Anhydrides | A number of reagents used to prepare carboxamides via a carboxylic−phosphoric anhydride intermediate have been reexamined. It was found that a simple carboxylic−phosphoric anhydride prepared from a carboxylic acid and commercially available diethyl chlorophosphate provided several significant advantages over more compl... | 10.1021/op980205g | 0 |
Improved Stereoselective Synthesis of the β-Anomer of 1-[3,5-Bis-<i>O</i>-(<i>p</i>-chlorobenzoyl)-2-deoxy-<scp>d</scp>-ribofuranosyl]-5-iodo-2-pyrimidinone | The lack of stereochemical control has been a major hurdle in synthesizing β-nucleosides in large scale. This paper reports a study of the effects of different catalysts used in the synthesis of β-nucleosides. The effects of time and temperature on α- and β-anomers are illustrated in this paper. The yield and selectivi... | 10.1021/op980204o | 0 |
A Concise Two-Step Synthesis of Thalidomide | A two-step synthesis of thalidomide is presented. The sequence requires no purifications. Treatment of l -glutamine with N -carbethoxyphthalimide produces N -phthaloyl- l -glutamine. Cyclization of N -phthaloyl- l -glutamine to afford thalidomide is accomplished by treatment with CDI in the presence of a catalytic amou... | 10.1021/op980201b | 1 |
Preparation of 2-[(Aryl)methyl]sulfinyl-1<i>H</i>-imidazo[4,5-<i>c</i>]pyridine, Useful as an Antiosteoporotic Agent | A new process for the oxidation of 2-[(aryl)methyl]thio-1 H -imidazo[4,5- c ]pyridine to 2-[(aryl)methyl]sulfinyl-1 H -imidazo[4,5- c ]pyridine was achieved using NCS under mild condition. The reaction selectively affords the desired sulfoxide as the only product in high yield without further oxidation to the sulfone s... | 10.1021/op980184q | 0 |
Development of a Process for Triazine-Promoted Amidation of Carboxylic Acids | A process has been developed for the triazine-promoted amidation of carboxylic acids. We have identified 2,4,6-trichloro-1,3,5-triazine (cyanuric chloride) as a cost-effective reagent for this transformation. The procedure is a suitable alternative to traditional amidation processes when an acid chloride cannot be prep... | 10.1021/op980097y | 0 |
Fast Scale-Up Using Solid-Phase Chemistry | A novel approach using solid-phase chemistry for scale-up was developed. The method makes use of commercially available high-load Merrifield resin. Three representative solid-phase chemistries leading to a diketopiperazine, a tetramic acid, and a β-lactam were scaled-up effectively and resulted in products with good yi... | 10.1021/op9800966 | 1 |
Synthetic Process Development of Antitumor Agent KT6587, an Indolocarbazole Alkaloid K252a Derivative | A facile and large-scale preparation process of an antitumor agent KT6587 ( 2 ), derived from an indolocarbazole alkaloid K252a ( 1 ), has been developed. The new synthetic process requires four steps: (i) selective N -silylation of the amide group of 1 with tert -butyldimethylsilyl chloride, (ii) methylation of the hy... | 10.1021/op980087x | 0 |
Application of Oxathiazolidine-S-oxide Chemistry to the Large-Scale Single-Step Synthesis of an O-Arylethanolamine | Alternative routes to the arylethanolamine subunit of a development drug have been investigated. The selected route, involving O-alkylation of a phenol using N-benzyloxathiazolidine-S-oxide, was developed to give a process used successfully for pilot plant manufacture. | 10.1021/op9800865 | 1 |
Process Research and Development of Melatonin | A short, simple, and industrially feasible process for the preparation of melatonin ( N -acetyl-5-methoxy tryptamine), starting from phthalimide and 1-bromo-3-chloropropane, in essentially four steps is discussed. The present article elucidates the preparative process along with the impurity profile of each intermediat... | 10.1021/op9800820 | 1 |
A Kinetic Model of the Choline Chloride Synthesis | The process of ethylene oxide interaction with trimethylamine hydrochloride, giving choline chloride, has been studied. The reactions that proceed in the system were established. A kinetic model adequately describing the experimental data was developed. | 10.1021/op980080f | 0 |
Multikilogram-Scale Synthesis of a Biphenyl Carboxylic Acid Derivative Using a Pd/C-Mediated Suzuki Coupling Approach | Reaction of 4-bromo-3-methylaniline with 4-chlorobutyryl chloride/TEA and subsequent treatment of the resulting secondary amide intermediate with KO t -Bu gives 1-(4-bromo-3-methylphenyl)pyrrolidin-2-one in 65% yield. This procedure has been optimised (74−76% overall yield) and has been carried out on 41 molar scale. I... | 10.1021/op980079g | 1 |
Response to Comment on “An Ecofriendly Catalytic Route for the Preparation of Perfumery Grade Methyl Anthranilate from Anthranilic Acid and Methanol” | ADVERTISEMENT RETURN TO ISSUEPREVCommunication to Edi...Communication to EditorNEXTResponse to Comment on "An Ecofriendly Catalytic Route for the Preparation of Perfumery Grade Methyl Anthranilate from Anthranilic Acid and Methanol"G. D. Yadav and M. S. KrishnanView Author Information Chemical Engineering Division, Uni... | 10.1021/op980074j | 0 |
Comment on “An Ecofriendly Catalytic Route for the Preparation of Perfumery Grade Methyl Anthranilate from Anthranilic Acid and Methanol” | ADVERTISEMENT RETURN TO ISSUEPREVCommunication to Edi...Communication to EditorNEXTComment on “An Ecofriendly Catalytic Route for the Preparation of Perfumery Grade Methyl Anthranilate from Anthranilic Acid and Methanol”Keith TurnerView Author Information Kappa Tau Consulting, 12 The Avenue, Fairfield, Stockton-on-Tees... | 10.1021/op980073r | 0 |
Studies toward an Improved Process for <i>N</i><sup>4</sup>,<i>N</i><sup>4</sup>-Disubstituted-2-cyano-<i>N</i><sup>1</sup>,<i>N</i><sup>1</sup>-dimethyl-1<i>H</i>-imidazole-1,4-disulfonamides | The development of a practical and cost-effective process for the manufacture of the title fungicidal compounds is described. In particular, substantial improvements in the chlorosulfonation of imidazole, studies on the stability of various cyanating agents, and a novel formylation/oximation/dehydration sequence to int... | 10.1021/op9800717 | 0 |
A New and Convergent Synthesis of (2<i>S</i>)-7-(4,4‘-Bipiperidinylcarbonyl)-2,3,4,5- tetrahydro-4-methyl-3-oxo-1<i>H</i>-1,4-benzodiazepine-2-acetic Acid Using a Palladium-Catalysed Aminocarbonylation Reaction | Palladium-catalysed aminocarbonylation of a 7-bromo- or 7-iodo-1,4-benzodiazepine with N -Cbz-4,4‘-bipiperidine hydrochloride efficiently introduced the 7-(4,4‘-bipiperidinylcarbonyl) moiety of (2 S )-7-(4,4‘-bipiperidinylcarbonyl)-2,3,4,5-tetrahydro-4-methyl-3-oxo-1 H -1,4-benzodiazepine-2-acetic acid. | 10.1021/op980068n | 1 |
Process Optimization in the Synthesis of 9-[2-(Diethylphosphonomethoxy)ethyl]adenine: Replacement of Sodium Hydride with Sodium <i>tert</i>-Butoxide as the Base for Oxygen Alkylation | 9-[2-(Diethylphosphonomethoxy)ethyl]adenine (diethyl-PMEA), a key intermediate in the production of the antiviral drug adefovir dipivoxil, was originally produced via a process utilizing sodium hydride (NaH) to couple hydroxyethyl adenine with diethyl p -toluenesulfonyloxymethanephosphonate. The use of NaH presented sa... | 10.1021/op980067v | 1 |
The Bicyclo[3.2.0]heptan-<i>endo</i>-2-ol and Bicyclo[3.2.0]hept-3-en-6-one Approaches in the Synthesis of Grandisol: The Evolution of an Idea and Efforts to Improve Versatility and Practicality | In this paper we will disclose a chemistry story that started with a single molecule, the monoterpene grandisol, used in protecting cotton crops from an important pest, Anthonomus grandis Boheman. Initially, efforts were aimed at giving ever more practicality, versatility, and efficiency to a synthetic scheme that was ... | 10.1021/op9800663 | 1 |
Azolides in Organic Synthesis and Biochemistry By H. A. Staab, H. Bauer, and K. M. Schneider. Wiley-VCH: Weinheim, Germany. 1998. 502 pp. ISBN 3-527-29314-0. £95.00. | ADVERTISEMENT RETURN TO ISSUEPREVBook ReviewAzolides in Organic Synthesis and Biochemistry By H. A. Staab, H. Bauer, and K. M. Schneider. Wiley-VCH: Weinheim, Germany. 1998. 502 pp. ISBN 3-527-29314-0. £95.00.J. Ian GraysonCite this: Org. Proc. Res. Dev. 1998, 2, 6, 433–434Publication Date (Web):September 30, 1998Publi... | 10.1021/op980062y | 0 |
Process Research and Structural Studies on Nabumetone | A short, simple and economical process for large-scale preparation of nabumetone has been developed. The single-crystal structures of nabumetone and one of its key intermediates have been determined by X-ray diffraction studies. Two impurities have been isolated and characterised. | 10.1021/op980060d | 1 |
Application of Heterogeneous Acid Catalysts to the Large-Scale Synthesis of 2- and 3-(<i>p</i>-Methoxyphenyl)-6-methoxybenzo[<i>b</i>]thiophenes | 2-( p -Methoxyphenyl)-6-methoxybenzothiophene ( 3 ) was synthesized by acid-catalyzed cyclization and rearrangement of the β-ketosulfide precursor 1 . The use of Amberlyst 15 resin as a catalyst for the cyclization increased the isomer ratio from 75:25 to 88:12, compared to a conventional approach using polyphosphoric ... | 10.1021/op980059e | 0 |
Optimisation of the Preparation and Isolation of 5-Amino-2,4,6-triiodoisophthalic Acid Dichloride | A scaleable process for the chlorination of 5-amino-2,4,6-triiodoisophthalic acid to the corresponding acid chloride, a building block for the synthesis of iodinated X-ray contrast agents, has been developed. Two dimeric byproducts have been isolated and assigned structures consistent with an amide and an anhydride. Hy... | 10.1021/op980055+ | 0 |
Process Development of a Platelet Aggregation Inhibitor | A practical and efficient method for N -amination of piperazine via a nitrosoamine, suitable for a large scale synthesis, is described. This method involved the temporary transformation of an in situ prepared aminopiperazine to a hydrazone, allowing efficient separation of zinc salt byproducts from the system. Acylatio... | 10.1021/op980050c | 1 |
Process for the Capture and Reuse of the 4,4‘-Dimethoxytriphenylmethyl Group during Manufacturing of Oligonucleotides | In a standard amidite coupling-based automated oligonucleotide synthesis campaign, the 4,4‘-dimethoxytriphenylmethyl (DMT) protecting group is discarded as waste along with large amounts of dichloromethane. Herein, we report a straightforward and simple process for complete capture and recovery of the DMT group and dic... | 10.1021/op980048l | 0 |
Kinetics and Process Parameter Studies in Highly Selective Air Oxidation of Side-Chain Alkyl Groups in Picolines, 2-Methylnaphthalene, and Pseudocumene | Picolines, 2- methylnaphthalene, and pseudocumene were oxidized by air in acetic acid medium. Process parameters and kinetics of the reaction were studied from the viewpoint of proces research and development. Use of lithium chloride as the promoter was worth considering for this oxidation to obtain a higher rate of re... | 10.1021/op980047t | 0 |
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