C - Chemistry – Metallurgy – 07 – D
Patent
C - Chemistry, Metallurgy
07
D
C07D 217/26 (2006.01)
Patent
CA 2059908
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 (CO2R1)2CHNHCOR2, in which R1 is (C1-C4)- alkyl and R2 is H, (C1-C4)-alkyl or (C6-C12)-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- tetrahydroisoquinoline-3-carboxylic acid is esterified by means of benzyl alcohol and p-toluenesulfonic acid, reacted with D(-)mandelic acid to give benzyl (D)- 1,2,3,4- tetrahydroisoquinoline-3-carboxylate (D)-mandelate and benzyl (L)-1,2,3,4- tetrahydroisoquinoline-3-carboxylate (D)-mandelate or with L(+)mandelic acid to give benzyl (D)-1,2,3,4-tetrahydroisoquinoline-3-carboxylate (L)-mandelate and benzyl (L)-1,2,3,4-tetrahydroisoquinoline-3-carboxylate (L)-mandelate and then the compounds obtained are separated into the optical antipodes by fractional crystallization in an inert solvent and the enantiomers (D)- or (L)-1,2,3,4- tetrahydroisoquinoline-3-carboxylic acid are liberated by basic hydrolysis, the chiral auxiliary reagent being recovered.
Kammermeier Bernhard
Lerch Ulrich
Bereskin & Parr Llp/s.e.n.c.r.l.,s.r.l.
Hoechst Aktiengesellschaft
LandOfFree
Process for the preparation of racemic and optically active... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Process for the preparation of racemic and optically active..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Process for the preparation of racemic and optically active... will most certainly appreciate the feedback.
Profile ID: LFCA-PAI-O-1770662