PROCESS FOR THE PREPARATION OF RACEMIC AND OPTICALLY ACTIVE 1,2,3,4-TETRAHYDROISOQUINOLINE-3-CARBOXYLIC ACID

摘要

The present invention relates to dihalo-o-xylylene in the basic medium of the general formula (CO ₂ R ¹ ) ₂ CHNHCOR ² (wherein R ¹ is (C ₁ -C ₄ ) -alkyl and R ² is H, ( By dialkyl N-acylamidomalonates of C ₁ -C ₄ ) -alkyl or (C ₆ -C ₁₂ ) -aryl), ring cyclic with dicarboxylic acid esters, basic hydrolysis and post-treatment with acid Decarboxylation and then reaction in acidic medium to afford (D, L) -1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid, or dihalo-o-xylylene is closed in basic medium To obtain the dicarboxylic acid ester and react directly without separating in a one-pot process to give (D, L) -1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid, If necessary, 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-tetra After obtaining isoisoquinoline-3-carboxylate, the diastereomers are separated by column chromatography and subjected to basic hydrolysis to (D)-or (L) -1,2,3,4-tetrahydroisoquinoline-3 Obtaining carboxylic acids or esterifying (D, L) -1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid with benzyl alcohol and p-toluenesulfonic acid and reacting with D (-) mandelic acid Benzyl (D) -1,2,3,4-tetrahydroisoquinoline-3-carboxylate (D) -mandelate and benzyl (L) -1,2,3,4-tetrahydroisoquinoline-3-carboxyl Obtain rate (D) -mandelate or react with L (+) mandelic acid to yield benzyl (D) -1,2,3,4-tetrahydroisoquinoline-3-carboxylate (L) -mandelate and benzyl (L ) -1,2,3,4-tetrahydroisoquinoline-3-carboxylate (L) -mandelate is obtained, and then the obtained compound is fractionated and crystallized in an inert solvent and divided into optical colons Racemic and optionally active 1, which recovers chiral adjuvant by separating high enantiomer (D)-or (L) -1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid by basic hydrolysis. A method for producing 2,3,4-tetrahydroisoquinoline-3-carboxylic acid.