Process Development and Scale Up of a Glycine Antagonist

Autor:	Guillaume Roux, Fiona Rawlinson, Alcide Perboni, Michael Anthony Forth, Darren Caine, Adam Banks, Christopher Drake, Matthew E. Popkin, Jerome F. Hayes, John S. Carey, Asa Gladwin, Paolo Maragni, Gary F. Breen, David O. Morgan, Paul Oxley, Simone Guelfi
Rok vydání:	2009
Předmět:	chemistry.chemical_compound chemistry Bromide Hydrochloride Yield (chemistry) Heck reaction Organic Chemistry Wittig reaction Imine Organic chemistry Physical and Theoretical Chemistry Mannich reaction Kinetic resolution
Zdroj:	Organic Process Research & Development. 13:1130-1140
ISSN:	1520-586X 1083-6160
Popis:	A synthetic route amenable to large-scale synthesis of the glycine antagonist (2R,4E)-7-chloro-4-(2-oxo-1-phenyl-pyyrrolidin-3-ylidene)-1,2,3,4-tetrahydroquinoline-2-carboxylic acid, (2R,3R,4R,5S)-6-(methylamino)hexane-1,2,3,4,5-penta-ol 12 is presented. The route consists of four stages of chemistry. Stage 1 starts from 5-chloro-2-iodoaniline hydrochloride and is a three-step telescoped stage consisting of an imine formation with ethyl glyoxalate, Mannich reaction using vinyloxytrimethylsilane, and subsequent Wittig reaction with (2-oxo-1-phenyl-3-pyrrolidinyl)triphenylphosphonium bromide. The stage 1 product (4E)-2[(5-chloro-2-iodophenyl)amino]-4-(2-oxo-1-phenyl-pyrrolidin-3-ylidene)butanoic acid ethyl ester 17 is subjected to an enzyme-catalysed kinetic resolution to prepare the single (2R)-enantiomer 19 as the ethyl ester. Stage 3 is the intramolecular Heck reaction to yield (2R,4E)-7-chloro-4-(2-oxo-1-phenyl-pyrrolidin-3-ylidene)-1,2,3,4-tetrahydroquinoline-2-carboxylic acid ethyl ester 31. The final...
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::65eeaaa75ed92bd7ee297cccea3b6a82 https://doi.org/10.1021/op9001824 Zobrazit plný text záznamu