Synthesis of anti-Parkinson agent

摘要

The present invention relates to an improved process for synthesis of anti-Parkinson compound of formula (I) from commercially available (R)-benzyl glycidyl ether, wherein the compound obtained has enantiopurity greater than >98%. Formula (I) wherein R1 and R2 are each independently selected from hydrogen or halogen.;

主权项

1. A process for preparation of an enantiomer of compound of formula I wherein R1 and R2 are each independently selected from hydrogen or halogen, said process comprising; a. regio selective reducing an epoxide (R)-compound 2 in presence of a reducing agent to obtain a secondary alcohol (R)-compound 3; b. mesylating the secondary alcohol (R)-compound 3 of step (a) followed by reacting with NaN3 to obtain an azido derivative (S)-compound 4; c. hydrogenating/hydrogenolysis of the azido derivative (S)-compound 4 obtained in step (b) with Pd(OH)2 catalyst followed by N-nosylation using nosyl chloride under basic conditions to obtain amino alcohol (S)-compound 5; d. condensing amino alcohol (S)-compound 5 and alkyl iodide compound 9 in presence of a base and a solvent to obtain a coupled product (S)-compound 10; wherein R1 and R2 are each independently selected from hydrogen or halogen; wherein R1 and R2 are each independently selected from hydrogen or halogen; e. oxidizing the coupled product (S)-compound 10 using TEMPO or bleach conditions to obtain an acid (S)-compound 11; wherein R1 and R2 are each independently selected from hydrogen or halogen f. reacting the acid (S)-compound 11 of step (e) with ethylchlorofomate in presence of Et3N and a solvent followed by reaction with aqueous NH3 to obtain an amide (S)-compound 12; and wherein R1 and R2 are each independently selected from hydrogen or halogen g. treating said amide (S)-compound 12 with thiophenol in presence of a base and a solvent to obtain the enantiomer of compound of formula I.