Acetic acid Oxaprozin

Apart from the salicylates NSAIDs include several classes of weak acids like propionic acid derivatives such as ibuprofen, carprofen, fenbufen, fenoprofen, flurbiprofen, ketorolac, loxoprofen, naproxen, oxaprozin, tiaprofenic acid and suprofen. Phenylbutazone is the most important representative of the pyrazolon derivatives which have a bad reputation for their risk of potentially fatal bone-marrow toxicity. To the acetic acid derivatives belong in-domethacin, diclofenac and sulindac. Sulindac is a pro-drug with less toxicity than indomethacin. The enolic acids include piroxicam, droxicam and tenoxicam. Meloxicam is an analog of piroxicam and has a high selectivity for COX-2. 

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 ). 

FIGURE 13.9 Structure of Oxaprozin, an oxazole acetic acid. 

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