Paper
LIU Yanlong, HU Zhongyuan, XING Lei, GUO Yahui, LIU Fei*
An improved process of parecoxib sodium was reported. 1,2-Diphenylethan-1-one oxime was prepared from 1,2-diphenylethan-1-one via oximation with hydroxylamine hydrochloride, which was followed by a cyclization with acetic anhydride to give 5-methyl-3,4-diphenyl-4,5-dihydroisoxazol-5-ol with a yield of 85％. Then the latter was subjected to a dehydration with sodium hydroxide instead of trifluoroacetic acid as the dehydrant to afford 5-methyl-3,4-diphenylisoxazole, the yield was increased from 70％ to 82％. After reacting with chlorosulfonic acid, the corresponding product reacted directly with ammonia without purification, then the crude product was recrystallized in ethyl acetate to produce 4-(5-methyl-3-phenylisoxazol-4-yl)benzenesulfonamide, with the yield in this two-step reaction increased from 48％ to 75％. After reacting with propionic anhydride, water was added into the reaction solution, and N-[[4-(5-methyl-3-phenylisoxazol-4-yl)phenyl]sulfonyl]propionamide was precipitated from the reaction solution, and the yield was increased from 75％ to 95％. Finally, the target compound was obtained via a salification with sodium hydroxide in a purity of 99.98％, and the total yield was increased from 10.0％ to 42.5％.
