4'-nitrobenzyl 7-phenoxyacetamido-3-methylenecepham-4-carboxylate sulfoxide

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 4'-nitrobenzyl 7-phenoxyacetamido-3-methylenecepham-4-carboxylate sulfoxide
• 英文别名: p-nitrobenzyl 7-phenoxyacetamido-3-methylenecepham-4-carboxylate-1-oxide；p-nitrobenzyl 7-phenoxyacetamido-3-methylenecepham-4-carboxylate1-oxide；(4-nitrophenyl)methyl (6S)-3-methylidene-5,8-dioxo-7-[(2-phenoxyacetyl)amino]-5lambda4-thia-1-azabicyclo[4.2.0]octane-2-carboxylate；(4-nitrophenyl)methyl (6S)-3-methylidene-5,8-dioxo-7-[(2-phenoxyacetyl)amino]-5λ4-thia-1-azabicyclo[4.2.0]octane-2-carboxylate
• 化学式: C₂₃H₂₁N₃O₈S
• 分子量: 499.501
• InChiKey: HBKWKOGDTHDLLR-DXMAILLKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  35
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  167
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  4'-nitrobenzyl 7-phenoxyacetamido-3-methylenecepham-4-carboxylate sulfoxide 在 丙酸 作用下， 以 乙酸乙酯 、 丙酸酐 为溶剂， 生成 p-nitrobenzyl 7-phenoxyacetamido-3-propionyloxymethyl-2-cephem-4-carboxylate
  参考文献：
  名称：

  Process for preparing 3-acyloxymethyl-2-cephem compounds

  摘要：

  一种3-外消旋亚甲基头孢烯烷磺酰氧酯与式为##STR1##的羧酸及其相应的酐混合物在约70°C至约130°C的温度下反应，以产生相应的3-酰氧甲基-.DELTA..sup.2-头孢烯。该产物在制备抗生素活性头孢菌素中是有用的中间体。

  公开号：

  US04029651A1
• 作为产物：
  描述：

  [2S-(2alpha,5alpha,6beta)]-3,3-二甲基-7-氧代-6-(苯氧基乙酰氨基)-4-硫杂-1-氮杂双环[3.2.0]庚烷-2-羧酸 4-硝基苄基酯 4-氧化物 在 四氯化锡 N-氯代丁二酰亚胺 、 methyloxirane 作用下， 以 乙酸乙酯 、 甲苯 为溶剂， 生成 4'-nitrobenzyl 7-phenoxyacetamido-3-methylenecepham-4-carboxylate sulfoxide
  参考文献：
  名称：

  Method of preparation of 3-methylenecephams

  摘要：

  青霉素亚砜衍生的氮杂环丙烯磺酰氯和相关的磺酸衍生物通过与弗里德尔-克拉夫茨催化剂或交换阳离子形成剂反应，环化成3-亚甲基头孢菌素。

  公开号：

  US04052387A1

文献信息

• Sulfinyl halides and their preparation from penicillin sulfoxides
  申请人：Eli Lilly and Company

  公开号：US04081440A1

  公开（公告）日：1978-03-28

  A penicillin sulfoxide ester is reacted with an N-chloro halogenating agent at a temperature of from about 75.degree. C. to about 135.degree. C. to produce a novel 2-chlorosulfinylazetidin-4-one intermediate. The intermediate can be treated with stannic chloride to produce a 3-exomethylenecepham sulfoxide.

  一种青霉素亚砜酯与N-氯卤化剂在约75摄氏度至约135摄氏度的温度下反应，产生一种新型的2-氯亚砜基氮杂环丙烷-4-酮中间体。该中间体可经锡氯化物处理而生成3-外亚甲基头孢烯亚砜。
• Method for the preparation of 2-chloro sulfinyl azetidinones
  申请人：Lupin Laboratories, Ltd.

  公开号：US05604222A1

  公开（公告）日：1997-02-18

  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.

  一种改进的制备2-氯亚砜基氮杂环丁酮的方法，其化学式为：其中R为：氢；C.sub.1 -C.sub.3 烷基；卤代甲基；氰甲基；苯基；取代苯基；苯氧基，苄氧基或取代苄基；化学式R.sub.2 --O--的基团，其中R.sub.2为叔丁基、2,2,2-三氯乙基、苄基或取代苄基；化学式R.sub.3 --(O).sub.n --CH.sub.2的基团，其中R.sub.3为苯基或取代苯基。通过将具有通用化学式的青霉素亚砜酯与N-氯卤化试剂在惰性有机溶剂中反应制备2-氯亚砜基氮杂环丁酮。反应在碱金属、碱土金属、铵、季铵盐或其混合物的磷酸盐或氢磷酸盐的存在下进行。这些化合物在头孢克洛的生产中作为中间体，头孢克洛是一种强效抗菌化合物。
• Process for preparing a 3-exomethylenecepham sulfoxide from penicillin
  申请人：Eli Lilly and Company

  公开号：US04075203A1

  公开（公告）日：1978-02-21

  A penicillin sulfoxide ester is reacted with an N-chloro halogenating agent at a temperature of from about 75.degree. C. to about 135.degree. C. and in the presence of an alkylene oxide and calcium oxide to produce a 2-chlorosulfinylazetidin-4-one intermediate. The intermediate, upon separation from the alkylene oxide, calcium oxide, and any conversion products of both the alkylene oxide and calcium oxide, can be treated with stannic chloride to produce a 3-exomethylenecepham sulfoxide.

  一种青霉素亚砜酯与N-氯卤化剂在约75°C至约135°C的温度下，在烷氧基和氧化钙的存在下反应，产生2-氯亚砜基氮杂环丁酮中间体。该中间体在与烷氧基、氧化钙及其转化产物分离后，可以用氯化锡处理，产生3-外亚甲基头孢烯亚砜酯。
• An improved method for the preparation of 2-chloro sulfinyl azetidin-4-one
  申请人：LUPIN LABORATORIES LIMITED

  公开号：EP0659742A1

  公开（公告）日：1995-06-28

  An improved method for the preparation of 2-chloro sulfinyl azetidin-4-one of the general formula: wherein R is hydrogen; C₁-C₃ alkyl; halomethyl; cyanomethyl; phenyl, substituted phenyl, phenoxy, benzyloxy or substituted benzyl with the substituent group selected from halo, alkyl, alkoxy, protected hydroxy, nitro, cyano and trifluoromethyl; a group of the formula R₂ -- O -- wherein R₂ is t-butyl, 2,2,2- trichloroethyl, benzyl or substituted benzyl; a group of the formula R₃-(O)n-CH₂ wherein R₃ is phenyl or substi-tuted phenyl with the substituent group selected from halo, alkyl, alkoxy, protected hydroxy, nitro, cyano or trifluoromethyl, 2-thienyl, 3-thienyl, 2-furyl, 3-furyl or 1,4-cyclohexadienyl, and n is 0 or 1; or a substituted aryl alkyl group of of formula wherein R₄ has the same meaning as R₃ defined above and W is a protected hydroxy or protected amino group; and R₁ is a carboxylic acid protecting group selected from the group consisting of C₁-C₄ alkyl, 2,2,2-trihalo alkyl, benzyl, substituted benzyl, like p-nitrobenzyl, phenacyl, halo substituted phenacyl and benzhydryl, is disclosed. Such compound is prepared by reacting a penicillin sulfoxide ester of the general formula wherein R and R₁ 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 scavening amount of a phosphate or hydrogen phosphate of an alkali metal, alkaline earth metal, ammonium, quaternary ammonium or mixtures of any thereof. These compounds find application as an intermediate in the production of cefaclor which are powerful anti-bacterial compounds.

  一种制备通式为 2-氯亚磺酰基氮杂环丁烷-4-酮的改进方法： 其中 R 是氢；C₁-C₃ 烷基；卤代甲基；氰甲基；苯基、取代苯基、苯氧基、苄氧基或取代苄基，其取代基团选自卤代、烷基、烷氧基、受保护羟基、硝基、氰基和三氟甲基；式 R₂ -- O -- 的基团，其中 R₂ 是叔丁基、2,2,2-三氯乙基、苄基或取代苄基；式 R₃-(O)n-CH₂的基团，其中 R₃ 是苯基或亚苯基，其取代基团选自卤代、烷基、烷氧基、受保护羟基、硝基、氰基或三氟甲基、2-噻吩基、3-噻吩基、2-呋喃基、3-呋喃基或 1,4-环己二烯基，且 n 是 0 或 1；或式 R₃-(O)n-CH₂ 的取代芳基烷基。 其中，R₄ 与上文定义的 R₃ 意义相同，W 是受保护的羟基或受保护的氨基；R₁ 是羧酸保护基，选自由 C₁-C₄ 烷基、2,2,2-三卤代烷基、苄基、取代的苄基（如对硝基苄基）、苯酰基、卤代苯酰基和苯烃基组成的组。这种化合物的制备方法是将通式为 其中 R 和 R₁ 具有上文定义的含义，与 N-氯卤化剂在惰性有机溶剂中反应。该反应在有一定酸清除量的碱金属、碱土金属、铵、季铵或它们的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，头孢克洛是一种强效抗菌化合物。
• 3-Hydroxycephalosporin solvates and process for their production
  申请人：ELI LILLY AND COMPANY

  公开号：EP0014565B1

  公开（公告）日：1983-02-23