头孢泊肟酯的合成改进
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摘要
以D-7-ACA为原料,经甲基化、 N-酰化和酯化反应等合成了头孢泊肟酯。对反应温度、 pH值、原料配比和催化剂等因素进行了工艺优化。通过IR、1H NMR、13C NMR和ESI-MS确证了头孢泊肟酯及中间体的结构。该工艺操作简单,原料价廉易得,总收率54.9%,产品纯度98.4%,具有工业化应用前景。
Cefpodoxime proxetil( 1) was synthesized from D-7-ACA via the processes of methylation, N-acylation and esterification with a total yield of 54.9% and a purity of 98.4%. The affecting factors including the reaction temperature, pH value, the ratio of materials and the catalyst were investigated. The structures of the product and intermediates were characterized by IR,1 H NMR,13 C NMR and ESI-MS. The preparation process was simple in operation, low in raw material cost, and suitable for industrial production.
Cefpodoxime proxetil( 1) was synthesized from D-7-ACA via the processes of methylation, N-acylation and esterification with a total yield of 54.9% and a purity of 98.4%. The affecting factors including the reaction temperature, pH value, the ratio of materials and the catalyst were investigated. The structures of the product and intermediates were characterized by IR,1 H NMR,13 C NMR and ESI-MS. The preparation process was simple in operation, low in raw material cost, and suitable for industrial production.
引文
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[2] Fung-Tomc J C, Huczko E, Stickle T, et al. Antibacterial activities of cefprozil compared with those of 13 oral cephems and 3 macrolides[J]. Antmicrob Agents Chemother, 1995, 39(2):533-538.
[3]李家泰,侯杰,高磊,等.头孢泊肟酯治疗细菌性感染122例临床评价[J].中华内科杂志, 1994, 33(7):440-443.
[4] Rodriguez, J C, Hemandez R, Gonzalez M, et al. A rapid procedure to prepare cefotaxime[J]. Il Farmaco, 2000, 55(5):393-396.
[5] Debashish D, Vinod G. Method for manufacture of cephalosporin and intermediates there of:US, 856502[P].1999-01-05.
[6]张彦龙,常中.头孢泊肟酯的制备[J].应用科技, 2002, 29(8):55-56.
[7] Fischer G E, Defossa U, Ggerlach R, et al. Diastereomeres of3-eephem-4-carboxylic acid-1-iso-propoxycarbonyloxy ethylester and process for its preparation, EP:0531875A2[P].1993-03-17.
[8]杜敬星,肖孝辉,刘俊华,等. 1-碘乙基异丙基碳酸酯的合成[J].精细化工中间体, 2003, 33(5):30-31.
[9] Rodriguez J C, Hernandez R, Gonzalez M, et al. An improved method for preparation of cefpodoxime proxetil[J]. Il Farmaco,2003, 58(5):363-369.
[10]撒应福,任秉钧.头孢类抗生素的制备方法:中国, 1763046A[P]. 2006-04-26.
[11]姚元海,刘爱民,陈经伟.头孢泊肟酯的合成[J].中国医药工业杂志, 2008, 39(2):90-92.
[2] Fung-Tomc J C, Huczko E, Stickle T, et al. Antibacterial activities of cefprozil compared with those of 13 oral cephems and 3 macrolides[J]. Antmicrob Agents Chemother, 1995, 39(2):533-538.
[3]李家泰,侯杰,高磊,等.头孢泊肟酯治疗细菌性感染122例临床评价[J].中华内科杂志, 1994, 33(7):440-443.
[4] Rodriguez, J C, Hemandez R, Gonzalez M, et al. A rapid procedure to prepare cefotaxime[J]. Il Farmaco, 2000, 55(5):393-396.
[5] Debashish D, Vinod G. Method for manufacture of cephalosporin and intermediates there of:US, 856502[P].1999-01-05.
[6]张彦龙,常中.头孢泊肟酯的制备[J].应用科技, 2002, 29(8):55-56.
[7] Fischer G E, Defossa U, Ggerlach R, et al. Diastereomeres of3-eephem-4-carboxylic acid-1-iso-propoxycarbonyloxy ethylester and process for its preparation, EP:0531875A2[P].1993-03-17.
[8]杜敬星,肖孝辉,刘俊华,等. 1-碘乙基异丙基碳酸酯的合成[J].精细化工中间体, 2003, 33(5):30-31.
[9] Rodriguez J C, Hernandez R, Gonzalez M, et al. An improved method for preparation of cefpodoxime proxetil[J]. Il Farmaco,2003, 58(5):363-369.
[10]撒应福,任秉钧.头孢类抗生素的制备方法:中国, 1763046A[P]. 2006-04-26.
[11]姚元海,刘爱民,陈经伟.头孢泊肟酯的合成[J].中国医药工业杂志, 2008, 39(2):90-92.