Preparation of chiral 1,2,3,4-tetrahydro-6,7-dialkoxy-3-isoquinolinecarboxylic acid and derivatives

A process for preparation of (S)-1,2,3,4-Tetrahydro-6,7-dialkoxy-3-isoquinolinecarboxylic acid compounds and their derivatives of the formula 1

• wherein R1 is hydrogen, lower alkyl, C2-C12 acyl, or R1O together are methylenedioxy;
• R2 is hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, aryl, substituted aryl, aralkyl or substituted aralkyl group;
• R3 is hydrogen, C2-C12 acyl group, benzyl, alkoxylcarbonyl group, or aralkoxyl carbonyl group;
• the process comprising:
• (i) reacting Levodopa of formula 2 with formaldehyde or formaldehyde precursors to obtain (S)-1,2,3,4-Tetrahydro-6,7-dihydroxy-3-isoquinolinecarboxylic acid of formula 3;
• (ii) protecting the amino group of formula 3;
• (iii) alkylating the phenol groups of formula 4 to form compound of formula 5;
• and
• (iv) esterifying the carboxylic acid of formula 5 and optionally removing N-protecting group
• wherein P is alkoxycarbonyl, acyl, alkyl, aryl, silyl, selfenyl or sulfonyl.