Method for producing (2S,4R,9S)-octahydro-1H-indole-2-carboxylic acid and intermediate products therefor

US6559318B1 · kind B1 · utility

Assignee

• BASF SE

Inventors

• Klaus Ebel · Lampertheim, DE
• Frank Ohlbach · Mülheim an der Ruhr, DE
• Christoph Nubling · Haßloch, DE

Key dates

• Filing date: Feb 5, 2002
• Grant date: May 6, 2003
• Expiry date: Feb 5, 2022

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07D209/42
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

Abstract

Described is a process for the preparation of (2S, 4R, 9S)-octahydro-1H-indole-2-carboxylic acid, comprisinga) reacting a compound of the formula I(R1O)2CH—CH2—CH(OR2)2  I wherein R1 and R2 may be the same or different and represent each a C1-4-alkyl group, with water in the presence of an acidic catalyst,b) subjecting the obtained 3,3-dialkoxypropionaldehyde of formula II(R2O)2CH—CH2—CHO  II to a Henry-reaction with nitromethane,c) subjecting the obtained 4,4-dialkoxy-1-nitro-4-butanol of formula III(R1O)2CH—CH2—CHOH—CH2—NO2  III to a dehydrationd) converting the obtained nitroolefin IV with the aid of a Diels-Alder reaction into the corresponding trans-4-(2,2-dialkoxyethyl)-5-nitro-1-caclohexene Ve) hydrogenating the obtained substance V into the corresponding trans-4-(2,2-dialkoxyethyl)-5-amino-1-cyclohexane VIf) subjecting the compound VI to a resolution of racemate and obtaining the (1S, 2R)-1-amino-2-(2,2-dialkoxyethyl)-cyclohexane VII in enantiomerically pure form by enzymatic racemate resolution,g) hydrolysing the obtained compound VII to the corresponding aldehyde VIIIh) c…