公开(公告)号：US07511135B2

公开(公告)日：2009-03-31

申请号：US10532194

申请日：2003-10-27

Applicant: Om Dutt Tyagi ,  Santosh Kumar Richhariya ,  Rajesh Kumar Ramchandra Pawar ,  Yuvaraj Atmaram Chavan

Inventor： Om Dutt Tyagi ,  Santosh Kumar Richhariya ,  Rajesh Kumar Ramchandra Pawar ,  Yuvaraj Atmaram Chavan

IPC: C07D501/36

CPC classification number: C07D417/14

Abstract: A process for preparation of ceftiofur of formula (I) having purity greater than 97% is disclosed. The process comprises reacting [2-(2-aminothiazol-4-yl)]-2-syn-methoxyimino acetic acid-2-benzothiazolyl thioester of formula (II), with 7-amino-3-(2-furanylcarbonylthiomethyl)-3-cephem-4-carboxylic acid of formula (III) in the presence of a mixture of an water-immiscible inert organic solvent and water and in the presence of a organic base and isolating ceftiofur of formula (I) substantially free of impurities by, a) adding water to the reaction mixture and selectively partitioning the impurities in the organic phase and ceftiofur (I) in the form of a salt with the base in the aqueous phase, b) acidifying the aqueous phase containing ceftiofur (I) in the form of a salt with the base in the presence of a mixture containing a water-miscible and a water-immiscible organic solvent and in the presence of a saturated aqueous solution of an alkali or alkaline earth containing salt, to partition ceftiofur (I) in the organic phase, and c) isolating ceftiofur (I) of high purity and substantially free of impurities by evaporation of the organic solvent or precipitation by addition of a anti-solvent.

Abstract translation: 公开了制备具有大于97％纯度的式（I）头孢噻呋的方法。 该方法包括使式（II）的[2-（2-氨基噻唑-4-基）] - 2-顺式 - 甲氧基亚氨基乙酸-2-苯并噻唑基硫代酯与7-氨基-3-（2-呋喃基羰硫基甲基）-3 （III）的头孢-4-羧酸在水不混溶的惰性有机溶剂和水的混合物存在下，在有机碱的存在下，分离式（I）的头孢噻呋基本上不含杂质， a）向反应混合物中加入水，并在水相中选择性地分配有机相中的杂质和与碱的盐形式的头孢噻呋（I），b）以含有头孢噻呋（I）的形式酸化含有头孢噻呋 在含有水混溶性和与水不混溶的有机溶剂的混合物存在下，在含有碱或碱土金属盐的饱和水溶液的存在下，将碱与碱反应，从而将头孢噻吩（I） 有机相，和c）分离高纯度和实质的头孢噻呋（I） 通过蒸发有机溶剂或通过加入抗溶剂沉淀而不含杂质。

公开(公告)号：US20080207912A1

公开(公告)日：2008-08-28

申请号：US12150744

申请日：2008-04-30

Applicant: Om Dutt Tyagi ,  Santosh Kumar Richhariya ,  Rajesh Kumar Ramchandra Pawar ,  Yuvaraj Atmaram Chavan

Inventor： Om Dutt Tyagi ,  Santosh Kumar Richhariya ,  Rajesh Kumar Ramchandra Pawar ,  Yuvaraj Atmaram Chavan

IPC: C07D277/40

CPC classification number: C07D417/14

Abstract: A process for preparation of ceftiofur of formula (I) of high purity and substantially free from impurities is disclosed. The process comprises reacting [2-(2-aminothiazol-4-yl)]-2-syn-methoxyimino acetic acid-2-benzothiazolyl thioester of formula (II), with 7-amino-3-(2-furanylcarbonylthiomethyl)-3-cephem-4-carboxylic acid of formula (III) in the presence of a mixture of an water-immescible inert organic solvent and water and in the presence of a organic base and isolating ceftiofur of formula (1) substantially free of impurities by, d) adding water to the reaction mixture and selectively partitioning the impurities in the organic phase and ceftiofur (I) in the form of a salt with the base in the aqueous phase, e) acidifying the aqueous phase containing ceftiofur (I) in the form of a salt with the base in the presence of a mixture containing a water-miscible and a water-immiscible organic solvent and in the presence of a saturated aqueous solution of an alkali or alkaline earth containing salt, to partition ceftiofur (I) in the organic phase, and f) isolating ceftiofur (I) of high purity and substantially free of impurities by evaporation of the organic solvent or precipitation by addition of a co-solvent.

Abstract translation: 公开了一种制备高纯度且基本上不含杂质的式（I）头孢噻呋的方法。 该方法包括使式（II）的[2-（2-氨基噻唑-4-基）] - 2-顺式 - 甲氧基亚氨基乙酸-2-苯并噻唑基硫代酯与7-氨基-3-（2-呋喃基羰硫基甲基）-3 （III）的头孢-4-羧酸在水不溶性惰性有机溶剂和水的混合物存在下，在有机碱的存在下，分离基本上不含杂质的式（1）的头孢噻肟， d）向反应混合物中加入水，并在水相中选择性地分配有机相中的杂质和与碱的盐形式的头孢噻呋（I），e）以含有头孢噻呋（I）的形式酸化含有头孢噻呋 在含有水混溶性和与水不混溶的有机溶剂的混合物存在下，在含有碱或碱土金属盐的饱和水溶液的存在下，将碱与碱反应，从而将头孢噻吩（I） 有机相，和f）分离高纯度和实质的头孢噻呋（I） 通过蒸发有机溶剂或通过加入共溶剂沉淀而不含杂质。

公开(公告)号：US07064198B2

公开(公告)日：2006-06-20

申请号：US10468584

申请日：2001-07-25

Applicant: Vinod Kumar Kansal ,  Sunil Gurudatt Bhat ,  Tanguturi Venkata Marutikumar ,  Yuvaraj Atmaram Chavan ,  Ramanathan Sankaran

Inventor： Vinod Kumar Kansal ,  Sunil Gurudatt Bhat ,  Tanguturi Venkata Marutikumar ,  Yuvaraj Atmaram Chavan ,  Ramanathan Sankaran

IPC: C07D501/34 ,  C07D501/04

CPC classification number: C07D501/00

Abstract: A process for preparation of cefuroxime axetil of formula (I) of at least 96% purity and substantially free of analogous Δ2-isomer of formula (II) and other impurities. The process comprises reacting cefuroxime acid of formula (III) with (R,S)-1-acetoxyethyl bromide of formula (IV), and a Group I or II metal carbonate in the presence of a compound of formula (V), MmHnPqOr  (V) wherein M is Group I or II metal; m is 1, 2, 3; n is 0, 1, 2, or 4; q is 1 or 2; r is 4, 7 or 8; in the presence of a C1-4 alcohol and a polar tertiary amide solvent selected from N,N-dimethylacetamide, N,N-dimethylformamide, N,N-dimetheylpropionamide, N,N-diethylacetamide, N,N-diethylformamide and N,N-diethylpropionamide at a temperature ranging from about −30 to +30° C. and subjecting the product thus obtained to a desired step of purification.

Abstract translation: 制备具有至少96％纯度且基本上不含式（II）的类似的三异构体和其它杂质的式（I）头孢呋辛酯的方法。 该方法包括使式（III）的头孢呋辛酸与式（IV）的（R，S）-1-乙酰氧基乙基溴和I或II族金属碳酸盐在式（Ⅴ）化合物存在下反应， in-line-formula description =“In-line Formulas”end =“lead”？> M＆lt;＆lt;＆lt; n＆gt;＆lt;＆lt;＆lt; （V）<？in-line-formula description =“In-line Formulas”end =“tail”？>其中M是I或II族金属; m为1,2,3; n为0,1,2或4; q为1或2; r为4,7或8; 在C 1-4醇和极性叔胺溶剂的存在下，选自N，N-二甲基乙酰胺，N，N-二甲基甲酰胺，N，N-二甲酰基丙酰胺，N，N-二乙基乙酰胺，N ，N-二乙基甲酰胺和N，N-二乙基丙酰胺，温度范围为约-30至+ 30℃，并将所得产物经过所需的纯化步骤。