HCID 9923910, compound → HCID 18380205, compound

Participants

Reaction Steps

The reduction of the methyl N-(2-(2-thienyl)-2-oxoethyl)-o-chlorophenylglycinate 20 to the corresponding alcohol results in a mixture of diastereoisomeric alcohols methyl N-(2-(2-thienyl)-2-hydroxyethyl)-o-chlorophenylglycinate 21. Reaction with formaline provides the 5-(2-thienyl)-3-(methoxycarbonyl-o-chlorobenzyl)-1,3-oxazolidine 22. Rearrangement of the 5-(2-thienyl)oxazolidine 22 derivative occurs in dry HCl/DMF solution to produce the desired methyl α-(7-hydroxy-4,5,6,7-tetrahydro-5-thieno[3,2-c]pyridyl)-o-chlorophenylglycinate 23. Finally, the alcohol is reduced to the racemic 24 or dextrorotatory clopidogrel 2 by direct dehydroxylation, e.g. treatment with stannous chloride under acidic conditions. Alternatively, derivatization of hydroxyl group to a leaving group followed by reduction or stepwise elimination/reduction of the corresponding 4,5-dihydropyridyl intermediate is conducive to the synthesis of racemic 24 or dextrorotatory clopidogrel 2. Treatment with carbonyl diimidazole, heating, followed by sodium borohydride reduction is provided as a non-limiting example.

Provenance & Evidence