3-Chloro-4-oxo-4-phenyl-butyric acid | 68262-01-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-Chloro-4-oxo-4-phenyl-butyric acid
• 英文别名: 3-Chloro-4-oxo-4-phenylbutanoic acid
• CAS: 68262-01-1
• 化学式: C₁₀H₉ClO₃
• 分子量: 212.633
• InChiKey: ZWISCCPRPJTJHM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  54.4
• 氢给体数：
  1
• 氢受体数：
  3

文献信息

• [EN] PROCESS FOR THE PRODUCTION OF LISINOPRIL<br/>[FR] PROCEDE DE PRODUCTION DE LISINOPRIL
  申请人：EOS ECZACIBASI OZGUN KIMYASAL

  公开号：WO2004000874A1

  公开（公告）日：2003-12-31

  The present invention provides a process for preparing N2-[1(S)-ethoxycarbonyl-3-phenylpropyl]-N6-trifluoroacetyl-L-lysine and lisinopril thereof. Lisinopril shows excellent angiotensin converting enzyme inhibitor activity. Friedel-Crafts acylation of benzene with maleic anhydride in the presence of AlCl¿3? affords trans-β-benzoylacrylic acid. Treatment of benzoylacrylic acid with HCl gas in ethanol gives ethyl 2-chloro-4-oxo-4-phenylbutyrate in high yield. The coupling reaction between ethyl 2-chloro-4-oxo-4-phenylbutyrate and trifluoroacetyl-L-lysine benzyl ester in the presence of a base pair and sodium iodide produces alkyl lydine derivative with a good diastereoselectivity. Catalytic hydrogenation of lysine derivative with palladium gives N?2¿-[1(S)-ethoxycarbonyl-3-phenylpropyl]-N6-trifluoroacetyl-L-lysine. This intermediate is activated to form cyclic N-anhydride by using N,N-carbonyldiimidazole and coupled with L-proline methyl ester hydrochloride to give fully protected lisinopril derivative, which is converted into crude lisinopril by hydrolysis.

  本发明提供了一种制备N2-[1(S)-乙氧羰基-3-苯基丙基]-N6-三氟乙酰-L-赖氨酸及其琥珀酸二乙酯盐（Lisinopril）的方法。Lisinopril表现出优异的血管紧张素转换酶抑制活性。在AlCl3存在下，苯与马来酸酐进行Friedel-Crafts酰化反应，得到反式-β-苯甲酰丙烯酸。将苯甲酰丙烯酸与HCl气体在乙醇中处理，高收率得到乙酸2-氯-4-氧代-4-苯基丁酯。在碱对和碘化钠存在下，乙酸2-氯-4-氧代-4-苯基丁酯与三氟乙酰-L-赖氨酸苄酯进行偶联反应，产生具有良好对映选择性的烷基赖氨酸衍生物。使用钯进行催化氢化，得到N2-[1(S)-乙氧羰基-3-苯基丙基]-N6-三氟乙酰-L-赖氨酸。使用N,N-羰基二咪唑激活该中间体形成环状N-酐，并与L-脯氨酸甲酯盐偶联，形成完全保护的Lisinopril衍生物，通过水解转化为粗Lisinopril。
• Process for the production of lisinopril
  申请人：ASLAN TUNCER

  公开号：US20070093664A1

  公开（公告）日：2007-04-26

  The present invention provides a process for preparing N 2 -[1(S)-ethoxycarbonyl-3-phenylpropyl]-N 6 -trifluoroacetyl-L-lysine and lisinopril thereof. Lisinopril shows excellent angiotensin converting enzyme inhibitor activity. Friedel-Crafts acylation of benzene with maleic anhydride in the presence of AlCl 3 affords trans-β-benzoylacrylic acid. Treatment of benzoylacrylic acid with HCl gas in ethanol gives ethyl 2-chloro-4-oxo-4-phenylbutyrate in high yield. The coupling reaction between ethyl 2-chloro-4-oxo-4-phenylbutyrate and trifluoroacetyl-L-lysine benzyl ester in the presence of a base pair and sodium iodide produces alkyl lydine derivative with a good diastereoselectivity. Catalytic hydrogenation of lysine derivative with palladium gives N 2 -[1(S)-ethoxycarbonyl-3-phenylpropyl]-N 6 -trifluoroacetyl-L-lysine. This intermediate is activated to form cyclic N-anhydride by using N,N-carbonyldiimidazole and coupled with L-proline methyl ester hydrochloride to give fully protected lisinopril derivative, which is converted into crude lisinopril by hydrolysis.

  本发明提供了一种制备N2-[1（S）-乙氧羰基-3-苯基丙基]-N6-三氟乙酰-L-赖氨酸及其L-赖氨酸普利类的方法。L-赖氨酸普利类表现出优异的血管紧张素转换酶抑制剂活性。苯基与马来酸酐在AlCl3存在下的Friedel-Crafts酰化反应得到顺式-β-苯甲酰丙烯酸。将苯甲酰丙烯酸与乙醇中的HCl气体处理，可以高产率得到乙酸2-氯-4-氧代-4-苯基丁酯。在碱对和碘化钠存在下，乙酸2-氯-4-氧代-4-苯基丁酯与三氟乙酰-L-赖氨酸苄酯进行偶联反应，产生具有良好对映选择性的烷基赖氨酸衍生物。用钯进行催化氢化，得到N2-[1（S）-乙氧羰基-3-苯基丙基]-N6-三氟乙酰-L-赖氨酸。使用N，N-碳酰亚咪唑激活该中间体形成环状N-酐，并与L-脯氨酸甲酯盐酸盐偶联，得到完全保护的L-赖氨酸普利类衍生物，通过水解转化为粗制L-赖氨酸普利类。
• PROCESS FOR THE PRODUCTION OF LISINOPRIL
  申请人：EOS Eczacibasi Ozgun Kimyasal Urunler Sanayi Ve Ti Caret A.S.

  公开号：EP1513868B1

  公开（公告）日：2006-08-09
• JPS53111085A
  申请人：——

  公开号：JPS53111085A

  公开（公告）日：1978-09-28
• US3933838A
  申请人：——

  公开号：US3933838A

  公开（公告）日：1976-01-20