Generation of Tosyl Azide in Continuous Flow Using an Azide Resin, and Telescoping with Diazo Transfer and Rhodium Acetate-Catalyzed O-H Insertion.

ABSTRACT: Generation of tosyl azide 12 in acetonitrile in flow under water-free conditions using an azide resin and its use in diazo transfer to a series of aryl acetates are described. Successful telescoping with a rhodium acetate-catalyzed O-H insertion has been achieved, thereby transforming the aryl acetate 8 to α-hydroxy ester 10, a key intermediate in the synthesis of clopidogrel 11, without requiring isolation or handling of either tosyl azide 12 or α-aryl-α-diazoacetate 9, or indeed having significant amounts of either present at any point. Significantly, the solution of α-diazo ester 9 was sufficiently clean to progress directly to the rhodium acetate-catalyzed step without any detrimental impact on the efficiency of the O-H insertion. In add

SUBMITTER: O'Mahony RM 

PROVIDER: S-EPMC8689650 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature