methyl 4-chloro-4-fluoro-3-oxobutyrate | 199003-10-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 酮酸及其衍生物
• 英文名称: methyl 4-chloro-4-fluoro-3-oxobutyrate
• 英文别名: methyl 4-chloro-4-fluoro-3-oxobutanoate
• CAS: 199003-10-6
• 化学式: C₅H₆ClFO₃
• 分子量: 168.552
• InChiKey: ZMZGJVZVQYTGMW-UHFFFAOYSA-N

物化性质

• 沸点：
  178.4±25.0 °C(Predicted)
• 密度：
  1.307±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  10
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 4-chloro-4-fluoro-3-oxobutyrate 在 硝酸异戊酯 、 乙酰氯 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 生成 methyl (Z)-2-(2-amino-5-fluorothiazol-4-yl)-2-(hydroxyimino)acetate
  参考文献：
  名称：

  Orally Active Cephalosporins. Part 4: Synthesis, Structure–Activity Relationships and Oral Absorption of Novel 3-(4-Pyrazolylmethylthio)cephalosporins with Various C-7 Side Chains

  摘要：

  A series of 3-(4-pyrazolylmethylthio)cephalosporins with various C-7 side chains was designed, synthesized and evaluated for antibacterial activity and oral absorption in rats. Antibacterial activity against Haemophilus influenzae was markedly increased by the C-7 oxime moiety. Deamination at the 2 position of, or introduction of a substituent such as halogen or methyl to, the 5 position of the (Z)-2-(2-aminothiazol-4-yl)-2-(hydroxyimino) moiety improved oral absorption. Among these compounds, FR192752 (40a) having a (Z)-2-(2-amino-5-chlorothiazol-4-yl)-2-hydroxyiminoacetam do moiety, showed potent antibacterial activity against both Gram-positive and Gram-negative bacteria including H. influenzae and penicillin G-resistant Streptococcus pneumoniae (PRSP). Further, it showed higher oral absorption than CFDN and FK041. (C) 2002 Elsevier Science Ltd, All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00416-3
• 作为产物：
  描述：

  甲醇 、 氯氟乙酸乙酯 、 丙二酸二异丙酯 在 氯磺酸 、 邻苯二甲酰氯 、 吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 11.0h， 以36%的产率得到methyl 4-chloro-4-fluoro-3-oxobutyrate
  参考文献：
  名称：

  Orally Active Cephalosporins. Part 4: Synthesis, Structure–Activity Relationships and Oral Absorption of Novel 3-(4-Pyrazolylmethylthio)cephalosporins with Various C-7 Side Chains

  摘要：

  A series of 3-(4-pyrazolylmethylthio)cephalosporins with various C-7 side chains was designed, synthesized and evaluated for antibacterial activity and oral absorption in rats. Antibacterial activity against Haemophilus influenzae was markedly increased by the C-7 oxime moiety. Deamination at the 2 position of, or introduction of a substituent such as halogen or methyl to, the 5 position of the (Z)-2-(2-aminothiazol-4-yl)-2-(hydroxyimino) moiety improved oral absorption. Among these compounds, FR192752 (40a) having a (Z)-2-(2-amino-5-chlorothiazol-4-yl)-2-hydroxyiminoacetam do moiety, showed potent antibacterial activity against both Gram-positive and Gram-negative bacteria including H. influenzae and penicillin G-resistant Streptococcus pneumoniae (PRSP). Further, it showed higher oral absorption than CFDN and FK041. (C) 2002 Elsevier Science Ltd, All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00416-3

文献信息

• Cephem compounds
  申请人：Fujisawa Pharmaceutical Co., Ltd.

  公开号：US06159961A1

  公开（公告）日：2000-12-12

  A compound of the formula: ##STR1## wherein R.sup.1 is amino or protected amino, R.sup.2 is hydrogen or hydroxy protective group, R.sup.3 is carboxy or protected carboxy, R.sup.4 is hydrogen, lower alkenyl, acyloxy(lower)alkenyl, optionally substituted heterocyclic(lower)alkenyl, optionally substituted heterocyclic(lower)alkenylthio, optionally substituted heterocyclic(lower)alkylthio, or optionally substituted heterocyclic-thio(lower)alkylthio and R5 is halogen or lower alkyl and pharmaceutically acceptable salts thereof, which is useful as a medicament for prophylactic and therapeutic treatment of infectious diseases.

  一种化合物的公式：##STR1## 其中R.sup.1是氨基或保护氨基，R.sup.2是氢或羟基保护基，R.sup.3是羧基或保护羧基，R.sup.4是氢、低烯基、酰氧（低）烯基、可选择取代的杂环（低）烯基、可选择取代的杂环（低）烯基硫、可选择取代的杂环（低）烷硫、或可选择取代的杂环硫（低）烷硫，R5是卤素或低烷基，以及其药学上可接受的盐，用于预防和治疗传染病的药物。
• NEW CEPHEM COMPOUNDS
  申请人：FUJISAWA PHARMACEUTICAL CO., LTD.

  公开号：EP0854875A1

  公开（公告）日：1998-07-29
• US5958914A
  申请人：——

  公开号：US5958914A

  公开（公告）日：1999-09-28
• US6159961A
  申请人：——

  公开号：US6159961A

  公开（公告）日：2000-12-12
• [EN] NEW CEPHEM COMPOUNDS<br/>[FR] NOUVEAUX COMPOSES DE CEPHEME
  申请人：FUJISAWA PHARMACEUTICAL CO., LTD.

  公开号：WO1997012890A1

  公开（公告）日：1997-04-10

  (EN) A compound of general formula (I) wherein R1 is amino or protected amino, R2 is hydrogen or hydroxy protective group, R3 is carboxy or protected carboxy, R4 is hydrogen, lower alkenyl, acyloxy(lower)alkenyl, optionally substituted heterocyclic(lower)alkenyl, optionally substituted heterocyclic(lower)alkenylthio, optionally substituted heterocyclic(lower)alkylthio, or optionally substituted heterocyclic-thio(lower)alkylthio and R5 is halogen or lower alkyl and pharmaceutically acceptable salts thereof, which is useful as a medicament for prophylactic and therapeutic treatment of infectious diseases.(FR) L'invention porte sur un composé représenté par la formule (I), dans laquelle R1 représente amino ou amino protégé; R2 représente un groupe inhibant hydrogène ou hydroxy; R3 représente carboxy ou carboxy protégé; R4 représente hydrogène, alcényle inférieur, acyloxy alcényle (inférieur), alcényle (inférieur) hétérocyclique facultativement substitué, alcénylthio (inférieur) hétérocyclique facultativement substitué, alcoylthio (inférieur) hétérocyclique facultativement substitué, ou thio alcoylthio (inférieur) hétérocyclique facultativement substitué, et R5 représente halogène ou alcoyle inférieur, et leurs sels pharmaceutiquement acceptables; ce composé étant un médicament pouvant être utilisé pour le traitement préventif et curatif de maladies infectieuses.