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用价廉易得的2-氰基-4’-溴甲基联苯为原料,与由叠氮钠和三乙胺盐酸盐原位反应生成的三乙胺叠氮酸盐经亲核取代反应、[3+2]偶极环加成同时引入叠氮基和四唑基,生成的4′-叠氮甲基-2-(1H-四唑-5-基)-1,1′-联苯和三苯膦经Staudinger反应制得沙坦类药物关键中间体4′-氨基甲基-2-(1H-四唑-5-基)-1,1′-联苯盐酸盐,总收率约72%,纯度99.88%。经300 kg规模验证适于工业化生产。
Using inexpensive 2-cyano-4’-bromomethylbiphenyl as starting material, nucleophilic substitution was carried out with the triethylamine azide salt formed by in situ reaction of sodium azide and triethylamine hydrochloride Reaction, the [3 + 2] dipolar cycloaddition is introduced into the azido and tetrazolyl groups simultaneously to form 4’-azidomethyl-2- (1H-tetrazol-5-yl) Biphenyl and triphenylphosphine by Staudinger reaction to make the key intermediate of sartan 4’-aminomethyl-2- (1H-tetrazol-5-yl) -1,1’-biphenyl hydrochloride, total About 72% yield, purity 99.88%. The 300 kg scale verified for industrial production.