公开(公告)号：US07064198B2

公开(公告)日：2006-06-20

申请号：US10468584

申请日：2001-07-25

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

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

IPC分类号： C07D501/34 ,  C07D501/04

CPC分类号： C07D501/00

摘要： 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.

摘要翻译： 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。

公开(公告)号：US5578721A

公开(公告)日：1996-11-26

申请号：US273309

申请日：1994-07-11

申请人： Niranjan L. Gupta ,  Ramanathan Sankaran ,  Shibu Varughese ,  Sakina Sitabkhan

发明人： Niranjan L. Gupta ,  Ramanathan Sankaran ,  Shibu Varughese ,  Sakina Sitabkhan

IPC分类号： C07D501/00 ,  C07D501/08 ,  C07D501/22 ,  C07D501/02

CPC分类号： C07D501/00 ,  Y02P20/55

摘要： A process for the manufacture of 3-exomethylene cepham sulfoxide ester of the formula ##STR1## wherein R is hydrogen, C.sub.1 -C.sub.3 alkyl, halomethyl, phenyl, substituted phenyl cyanomethyl, phenoxy, benzyloxy or substituted benzyl with a substituent group such as that selected from halo, alkyl, alkoxy, protected hydroxy, nitro, cyano and trifiuoromethyl, a group of the formula R.sub.2 --0-- wherein R.sub.2 is t-butyl, 2,2,2-trichloro ethyl, benzyl or substituted benzyl; a group of the formula R.sub.3 --[0].sub.n --CH.sub.2, wherein R.sub.3 is phenyl or substituted phenyl with the substituent group selected from halo, alkyl, alkoxy, protected hydroxy, nitro, cyano, or 1,4-cyclohexadienyl, and n is 0 or 1; or a substituted arylalkyl group of formula R.sub.4 --CH where R.sub.4 has the same meaning as R.sub.3 defined above and W is a protected hydroxy or protected amino group; and R.sub.1 is a carboxylic acid protecting group such as that selected from the group consisting of C.sub.1 -C.sub.4 alkyl, 2,2,2-trihalo alkyl, benzyl, substituted benzyl such as para nitrobenzyl, phenacyl, halo substituted phenacyl and benzhydryl is disclosed. Such compound is prepared by reacting a chlorosulfinylazetidinone of the formula ##STR2## wherein R and R.sub.1 have the same meanings as defined above, with a Lewis Acid type Friedel-Crafts catalyst and a sulfur compound in an inert solvent under anhydrous condition. These compounds find application as an intermediate for the preparation of cephalosporin antibiotics.

摘要翻译： 其中R为氢，C 1 -C 3烷基，卤代甲基，苯基，取代的苯基氰基甲基，苯氧基，苄氧基或取代的苄基，其具有如下选择的取代基的制备式（I）的3-异亚甲基头孢烯亚砜酯的方法： 卤素，烷基，烷氧基，保护的羟基，硝基，氰基和三氟甲基，式R2-0-基团，其中R2是叔丁基，2,2,2-三氯乙基，苄基或取代的苄基; 式R 3 - [O] n -CH 2的基团，其中R 3是苯基或具有选自卤素，烷基，烷氧基，保护的羟基，硝基，氰基或1,4-环己二烯基的取代基的取代苯基，n是 0或1; 或式R4-CH的取代芳基烷基，其中R4具有与上述定义的R3相同的含义，W是受保护的羟基或被保护的氨基; 并且R 1是羧酸保护基，例如选自C 1 -C 4烷基，2,2,2-三卤代烷基，苄基，取代的苄基如对硝基苄基，苯甲酰甲基，卤素取代的苯甲酰甲基和二苯甲基的羧酸保护基。 通过在无水条件下，在惰性溶剂中使路易斯酸型Friedel-Crafts催化剂和硫化合物与式（VII）中R和R 1具有与上述定义相同的式的氯亚磺酰基氮杂环丁酮反应来制备该化合物。 这些化合物可用作制备头孢菌素抗生素的中间体。

公开(公告)号：US5604222A

公开(公告)日：1997-02-18

申请号：US173757

申请日：1993-12-27

申请人： Niranjan L. Gupta ,  Ramanathan Sankaran ,  Sakina Sitabkhan

发明人： Niranjan L. Gupta ,  Ramanathan Sankaran ,  Sakina Sitabkhan

IPC分类号： C07D205/095 ,  C07D409/12 ,  C07D499/04 ,  C07D501/00 ,  C07D501/10 ,  C07D501/14

CPC分类号： C07D409/12 ,  C07D205/095 ,  C07D501/00 ,  Y02P20/55

摘要： An improved method for the preparation of 2-chloro sulfinyl azetidin-4-one of the formula: ##STR1## wherein R is: hydrogen; C.sub.1 -C.sub.3 alkyl; halomethyl; cyanomethyl; phenyl; substituted phenyl; phenoxy, benzyloxy- or substituted benzyl; a group of the formula R.sub.2 --O--wherein R.sub.2 is t-butyl, 2,2,2-trichloroethyl, benzyl or substituted benzyl; a group of the formula R.sub.3 --(O).sub.n --CH.sub.2 wherein R.sub.3 is phenyl or substituted phenyl. The 2-chlorosulfinylazetidin-4-one is prepared by reacting a penicillin sulfoxide ester of the general formula ##STR2## wherein R and R.sub.1 have the meanings defined above with an N-chloro halogenating agent in an inert organic solvent. The reaction is carried out in the presence of an acid scavenging amount of a phosphate or hydrogen phosphate of an alkali metal, alkaline earth metal, ammonium, quaternary ammonium or mixtures thereof. These compounds find application as intermediates in the production of cefaclor which are powerful anti-bacterial compounds.

摘要翻译： 用于制备下式的2-氯亚磺酰基氮杂环丁烷-4-酮的改进方法：; 氰甲基 苯基; 取代的苯基; 苯氧基，苄氧基或取代的苄基; 式R2-O-的基团，其中R2是叔丁基，2,2,2-三氯乙基，苄基或取代的苄基; 式R 3 - （O）n -CH 2的基团，其中R 3是苯基或取代的苯基。 2-氯亚磺酰基氮杂环丁烷-4-酮的制备方法是将惰性有机溶剂中通式为“IMAGE”的青霉素亚砜酯，其中R和R 1具有上述定义与N-氯卤化剂反应。 该反应在酸清除量的碱金属，碱土金属，铵，季铵或其混合物的磷酸盐或磷酸氢盐存在下进行。 这些化合物可用作生产头孢克洛的中间体，它们是强大的抗菌化合物。

公开(公告)号：US5824801A

公开(公告)日：1998-10-20

申请号：US908016

申请日：1997-08-11

申请人： Niranjan Lal Gupta ,  Ramanathan Sankaran ,  Sugata Chattejee ,  Tumma Hari Krishna

发明人： Niranjan Lal Gupta ,  Ramanathan Sankaran ,  Sugata Chattejee ,  Tumma Hari Krishna

IPC分类号： C07D501/00 ,  C07D501/14 ,  C07D501/59

CPC分类号： C07D501/00

摘要： A process for the stereospecific synthesis of keto-enol tautomeric mixture of p-nitrobenzyl (1R,6R,7R)-7-phenoxyacetamido-3-oxo-3-cepham-4-(R/S)-carboxylate-1-oxide and p-nitrobenzyl (1R,6R,7R)-7-phenoxyacetamido-3-hydroxy-3-cephem-4-carboxylate-1-oxide is described. These compounds are valuable intermediates for the synthesis of cephalosporin antibiotics e.g. cefaclor.

摘要翻译： （1R，6R，7R）-7-苯氧基乙酰氨基-3-氧代-3-头孢烯-4-（R / S） - 羧酸-1-氧化物对硝基苄基酮的酮 - 烯醇互变异构体混合物的立体有择合成方法和 描述了（1R，6R，7R）-7-苯氧基乙酰氨基-3-羟基-3-头孢烯-4-羧酸-1-氧化物对硝基苄酯。 这些化合物是合成头孢菌素抗生素的有价值的中间体，例如 头孢克洛

公开(公告)号：US5750683A

公开(公告)日：1998-05-12

申请号：US618533

申请日：1996-03-19

申请人： Niranjan Lal Gupta ,  Ramanathan Sankaran ,  Sugata Chattejee ,  Tumma Hari Krishna

发明人： Niranjan Lal Gupta ,  Ramanathan Sankaran ,  Sugata Chattejee ,  Tumma Hari Krishna

IPC分类号： C07D501/00 ,  C07D501/14 ,  C07D501/59 ,  C07D501/20

CPC分类号： C07D501/00

摘要： A process for the stereospecific synthesis of keto-enol tautomeric mixture of p-nitrobenzyl(1R,6R,7R)-7-phenoxyacetamido-3-oxo-3-cepham-4-(R/S)-carboxylate-1-oxide and p-nitrobenzyl(1R,6R,7R)-7-phenoxyacetamido-3-hydroxy-3-cephem-4-carboxylate-1-oxide is described. This process comprises a) reaction of 7-phenoxyacetamido-3-exomethylene-cepham-4-carboxylic acid p-nitrobenzyl ester with ozone in a inert solvent such as acetone, or methylethyl ketone optionally in the presence of a protic solvent such as methanol, acetic acid or isopropanol at a temperature ranging from -90.degree. C. to -40.degree. C. to give the corresponding ozonide and, b) decomposition of the ozonide to keto-enol tautomeric mixture of p-nitrobenzyl(1R,6R,7R)-7-phenoxyacetamido-3-oxo-3-cepham-4-(R/S)-carboxylate-1-oxide and p-nitrobenzyl(1R,6R,7R)-7-phenoxyacetamido-3-hydroxy-3-cephem-4-carboxylate-1-oxide without use of any reducing agent. This keto-enol tautomeric mixture is a valuable intermediate for the synthesis of cephalosporin antibiotics e.g. cefaclor.

摘要翻译： （1R，6R，7R）-7-苯氧基乙酰氨基-3-氧代-3-头孢烯-4-（R / S） - 羧酸-1-氧化物对硝基苄基酮的酮 - 烯醇互变异构体混合物的立体有择合成方法和 描述了（1R，6R，7R）-7-苯氧基乙酰氨基-3-羟基-3-头孢烯-4-羧酸-1-氧化物对硝基苄酯。 该方法包括：a）7-苯氧基乙酰胺基-3-异亚甲基 - 头孢烯-4-羧酸对硝基苄基酯与惰性溶剂如丙酮或甲基乙基酮的反应，任选地在质子溶剂如甲醇， 乙酸或异丙醇，温度范围为-90℃至-40℃，得到相应的臭氧化物，和b）将臭氧化物分解成（1R，6R，7R）对硝基苄基酮的酮 - 烯醇互变异构体混合物， （R，S） - 羧酸-1-氧化物和（1R，6R，7R）-7-苯氧基乙酰胺基-3-羟基-3-头孢烯-4-酮 4-羧酸酯-1-氧化物，不使用任何还原剂。 这种酮 - 烯醇互变异构体混合物是用于合成头孢菌素抗生素的有价值的中间体。 头孢克洛