一种头孢地尼侧链酯的制备方法
|
摘要
以(Z)-2-(2-氨基-4-噻唑基)-2-羟基亚胺乙酸乙酯和三苯基甲醇为原料,在碳酸二甲酯溶剂和碳酸二甲酯三氟化硼络合物催化下进行反应,反应完全后减压蒸去溶剂,加甲醇固化析晶,中间产物用片碱水解脱去乙酯,盐酸酸化,得到2-(2-氨基-4-噻唑)-2-(Z)-三苯基甲氧亚胺基乙酸。2-(2-氨基-4-噻唑)-2-(Z)-三苯基甲氧亚胺基乙酸与二硫化二苯骈噻唑,在亚磷酸三乙酯和三乙胺催化下进行酯化得到(Z)-硫代苯骈噻唑-2-(2-氨基-4-噻唑)-三苯甲基氧亚胺基乙酸活性酯,总收率为80.4%。方法操作简单,溶媒低毒易回收,成本低,得到产物纯度高,具有工业化生产前景。
2-(2-Amino-4-thiazolyl)-2-(Z)-triphenyl-methoxyimino acetic acid was obtained using(Z)-2-(2-aminothiazol-4-yl)-2-hydroxyimino ethyl acetate and triphenyl methanol as raw materials, dimethyl carbonate as solvent and dimethyl carbonate boron trifluoride complex as catalyst. This reaction was carried out through a process including solvent evaporation under reduced pressure, crystallization from methanol, caustic hydrolysis and acidification using hydrochloric acid.(Z)-Thiobenzothiazole-2-(2-amino-4-thiazolyl)-trityloxyimino acetic acid active ester was obtained from esterification reaction of 2-(2-Amino-4-thiazolyl)-2-( Z)-triphenyl methoxyimino acetic acid with diphenyl disulfide benzothiazole using triethylphosphite and triethylamine as catalyst. This method is simple, solvents easy to recycle and low toxicity, low cost, to obtain high purity and suitable for industrial production.
2-(2-Amino-4-thiazolyl)-2-(Z)-triphenyl-methoxyimino acetic acid was obtained using(Z)-2-(2-aminothiazol-4-yl)-2-hydroxyimino ethyl acetate and triphenyl methanol as raw materials, dimethyl carbonate as solvent and dimethyl carbonate boron trifluoride complex as catalyst. This reaction was carried out through a process including solvent evaporation under reduced pressure, crystallization from methanol, caustic hydrolysis and acidification using hydrochloric acid.(Z)-Thiobenzothiazole-2-(2-amino-4-thiazolyl)-trityloxyimino acetic acid active ester was obtained from esterification reaction of 2-(2-Amino-4-thiazolyl)-2-( Z)-triphenyl methoxyimino acetic acid with diphenyl disulfide benzothiazole using triethylphosphite and triethylamine as catalyst. This method is simple, solvents easy to recycle and low toxicity, low cost, to obtain high purity and suitable for industrial production.
引文
[1]Walte r G.A process for the preparation of cephlosporins side Chains:PCT,2003040116[P].2003-05-15.
[2]付德才.2-(2-氨基-4-噻唑)-2(Z)-三苯甲氧亚氨基乙酸的制备方法:中国,102180843A[P].2011-03-02.
[3]朱阳,刘国庆.(Z)-2-(2-氨基噻唑-4-基)-2-三苯甲氧基亚胺基乙酸合成的改进[J].中国医药工业杂志,1997,28(6):270-271.
[4]Elisobeth D.Synthesis of HR 916 K.An efficient route to the pure diastereomers of the 1-(pivaloyloxy)ethyl esters of cephalosporins[J].Liebigs Annalen,1996,11:1 743-1 949.
[5]Shinichiro F.Production of protected hydroxy group-containing heterocyclic compound:JP,07097368[P].1995-04-11.
[6]Senthilkumar.Intermediate in the preparation of cephalosporin antibiotic:IN,2007CH03159[P].2010-03-19.
[7]Walter C.A process for the preparation of cephalosporins side chains:PCT,2003040116[P].2003-05-15.
[8]Cho I S.Preparation of cephalosporin antibiotics:US,5859256[P].1999-01-12.
[9]Dai D M.Preparation of 2-aminothiazol-4-yl-acetic acid derivatives:WO,2011029596[P].2011-03-17.
[2]付德才.2-(2-氨基-4-噻唑)-2(Z)-三苯甲氧亚氨基乙酸的制备方法:中国,102180843A[P].2011-03-02.
[3]朱阳,刘国庆.(Z)-2-(2-氨基噻唑-4-基)-2-三苯甲氧基亚胺基乙酸合成的改进[J].中国医药工业杂志,1997,28(6):270-271.
[4]Elisobeth D.Synthesis of HR 916 K.An efficient route to the pure diastereomers of the 1-(pivaloyloxy)ethyl esters of cephalosporins[J].Liebigs Annalen,1996,11:1 743-1 949.
[5]Shinichiro F.Production of protected hydroxy group-containing heterocyclic compound:JP,07097368[P].1995-04-11.
[6]Senthilkumar.Intermediate in the preparation of cephalosporin antibiotic:IN,2007CH03159[P].2010-03-19.
[7]Walter C.A process for the preparation of cephalosporins side chains:PCT,2003040116[P].2003-05-15.
[8]Cho I S.Preparation of cephalosporin antibiotics:US,5859256[P].1999-01-12.
[9]Dai D M.Preparation of 2-aminothiazol-4-yl-acetic acid derivatives:WO,2011029596[P].2011-03-17.