Process for the preparation of racemic and optically active 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid and its precursors
US5252738A · kind A · utility
Assignee
Inventors
Key dates
| Filing date | Jan 21, 1992 |
| Grant date | Oct 12, 1993 |
| Priority date | — |
| Expiry date | Jan 21, 2012 |
Classification
- Technology area (CPC C)Chemistry; Metallurgy
- CPC primaryC07D217/26
- WIPO fieldOrganic fine chemistry
- WIPO sectorChemistry
Abstract
A process for the preparation of racemic and optically active 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid is described, in which dihalo-o-xylylenes are cyclized to dicarboxylic acid esters in basic medium using dialkyl N-acylamidomalonates of the formula (CO.sub.2 R.sup.1).sub.2 CHNHCOR.sup.2, in which R.sup.1 is (C.sub.1 -C.sub.4)-alkyl and R.sup.2 is H, (C.sub.1 -C.sub.4)-alkyl or (C.sub.6 -C.sub.12)-aryl, decarboxylated by basic hydrolysis and subsequent acid work-up and then reacted in acid medium to give (D,L)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid, or dihalo-o-xylylenes are cyclized in basic medium to give the dicarboxylic acid esters and these are reacted directly without isolation in a one-pot process to give (D,L)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid, if desired the racemic 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid is reacted with (-)menthol and p-toluenesulfonic acid to give (-)menthyl (D)- or (L)-1,2,3,4-tetrahydroisoquinoline-3-carboxylate, then the diastereomers are separated by column chromatography and subjected to basic hydrolysis to give (D)- or (L)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid, or (D,L)-1,2,3,4-tetrahydroisoqui…
Source: USPTO / EPO open patent data. Objective bibliographic and citation counts.