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    • 2. 发明授权
    • Process for preparing haloketo acid derivatives
    • 制备卤代酸衍生物的方法
    • US5268501A
    • 1993-12-07
    • US988432
    • 1992-12-09
    • Takaharu IkedaSeiichi KaiMasayoshi Minai
    • Takaharu IkedaSeiichi KaiMasayoshi Minai
    • C07C67/313C07C67/343C07C69/716C07C251/38C07C229/06
    • C07C251/38C07C67/313C07C67/343C07C69/716
    • Process for preparing haloketo acid derivatives [I]: ##STR1## wherein R is H or C.sub.1-6 alkyl, and X is chlorine or bromine, which comprises reacting .beta.-oxo-acid ester [II]: ##STR2## wherein R.sup.1 is H or C.sub.1-6 alkyl, R.sup.2 is C.sub.1-5 alkyl or OR.sup.3 (R.sup.3 is C.sub.1-6 alkyl), and X is the same as above, with nitrosating agent [IV]:ONOR.sup.4 [IV]wherein R.sup.4 is H, alkyl, halogen or SO.sub.3 H to give 7-halo-2-hydroxyminoheptanoic acid ester [III]: ##STR3## wherein R.sup.1 and X are the same as above, following 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.
    • 制备卤代羧酸衍生物的方法[I]:其中R是H或C 1-6烷基,X是氯或溴,其包括使β-氧代酸酯[II]: II]其中R 1是H或C 1-6烷基,R 2是C 1-5烷基或OR 3(R 3是C 1-6烷基),X与上述相同,与亚硝化剂[Ⅳ]:ONOR4 [Ⅳ]其中R4 是H,烷基,卤素或SO 3 H,得到7-卤代-2-羟基乙酸庚酯。[III]:其中R1和X与上述相同,然后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。