头孢尼西钠的合成

Synthesis of Cefonicid Sodium

7-氨基头孢烷酸(7-ACA)与5-巯基-1,2,3,4-四氮唑-1-甲基磺酸双钠盐(SMT-DS)在BF3作用下缩合,生成7-氨基-3-[甲磺酸基-1-H-四唑-5-基-巯甲基]-3-头孢烯4-羧酸(3)。3与D-(-)-甲酰基扁桃酸酰氯在pH6.5-7.0下酰化、盐酸作用下去甲酰基成头孢尼西酸,再与N,N-二苄基乙二胺二醋酸盐(DBED)结合生成头孢尼西胺盐(5)。5经酸化,成盐反应得头孢尼西钠。反应总收率为60.7%,所得产品纯度为98.7%(HPLC)。

7 - amino -3 - [ sulphomethyl - 1 - H - tetrazol - 5 - yl - thiomethyl ] - 3 - cephem - 4 - carboxylic （ 3 ） was synthesis by reaction of 7 - aminoeephalosporanic acid （7 - ACA） and 5 - mercapto - 1,2,3,4 -tetrazole disodium （SMT- DS） in presence of BF3. Cefonicid benzathine salts （6）via acylation of 3 and D - （ - ） - formylmandeloyl chloride at pH 6. 5 - 7. 0, deformylmandeloyl by treatement with hydrochloric acid , reaction with N, N - dibenzylethylene diamine diacetate （DBED）. Finally,the compound 6 followed by acid and salt yield cefonieid sodium （1）. The compound 1 was obtained in overall yield 60.7% with high purity[ above 98.7% （HPLC） ].