Benzoin Oxaprozin

It is traditionally prepared by esterification of benzoin 58 with subsequent cyclization of the ketoester 60 with the nitrogen-donating cyclization agent ammonium acetate (Scheme 25.9). The fact that production of oxaprozin requires elevated temperatures for several hours makes its synthesis attractive for use in our investigations using microwaves to decrease the reaction time and increase the overall yield. 

The two general procedures for cyclization of the keto ester 60 to 57 require heating with ammonium acetate (8 eq) in acetic acid or ammonium acetate (2 eq) in a mixture of acetic acid and formic acid for several (2 to 6) hours. Optimization of the reaction parameters (time, temperature, and ratio of the reaction components) afforded an 86% yield (HPLC) of oxaprozin when 63 was heated, with 8 eq of CH3COONH4 in acetic acid, at 150°C for 10 min. The overall isolated yield of oxaprozin 57 from benzoin 58 under microwave irradiation was 76% (versus 72% ) at significantly accelerated reaction speeds (15 min versus 10 h ). 

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