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    • 6. 发明公开
    • Process for preparing haloketo acid derivatives
    • 制备卤代酮酸衍生物的方法
    • EP0441371A1
    • 1991-08-14
    • EP91101678.0
    • 1991-02-07
    • SUMITOMO CHEMICAL COMPANY, LIMITED
    • Ikeda, TakaharuKai, SeiichiMinai, Masayoshi
    • C07C67/343C07C67/313C07C69/716C07C251/38
    • C07C69/716C07C67/313C07C67/343C07C251/38
    • Process for preparing haloketo acid derivatives [I]:

      wherein R is H or C₁₋₆ alkyl, and X is a chlorine or bromine, which comprises reacting β-oxo-acid ester [II]:

      wherein R¹ is C₁₋₆ alkyl, R² is C₁₋₅ alkyl or OR³ (R³ is C₁₋₆ alkyl), and X is the same as above, with nitrosating agent [IV]:



              ONOR⁴   [IV]



      wherein R⁴ is H, alkyl, halogen or SO₃H to give 7-halo-2-hydroxyiminoheptanoic acid ester [III]:

      wherein R¹ and X are the same as above, followed by reacting the product with aldehyde or ketone; and intermediates therefor, and process for preparing said intermediates. Said haloketo acid derivatives are useful as intermediate for synthesis of cilastatin, which is useful as medicament, especially as dehydropeptidase inhibitor.
    • 制备卤代酮酸衍生物[Ⅰ]的方法:其中R是H或C 1-6烷基,X是氯或溴,该方法包括使β-氧代酸酯[Ⅱ]:其中R 1是C 1-6烷基,R 2 其中R 4是H,烷基,卤素或SO 3 H,其中R 4是C 1-5烷基或OR 3(R 3是C 1-6烷基),X与上述相同,与亚硝基化试剂〔Ⅳ〕反应,得到7-卤代 -2-羟基亚氨基庚酸酯[Ⅲ]:其中R 1和X与上述相同,接着使产物与醛或酮反应; 及其中间体,以及制备所述中间体的方法。 所述卤代酮酸衍生物可用作合成西司他丁的中间体,其可用作药物,特别是作为脱氢肽酶抑制剂。