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    • 3. 发明授权
    • Process for the preparation of benzothiazepine derivatives
    • 苯并硫氮杂衍生物的制备方法
    • US4566995A
    • 1986-01-28
    • US718100
    • 1985-04-01
    • Chaim SimonovitchTheodor HoffmanSabar Sasson
    • Chaim SimonovitchTheodor HoffmanSabar Sasson
    • C07D281/10C07D281/02
    • C07D281/10
    • The present invention relates to a process for the preparation of benzothiazepine derivatives of general formula I ##STR1## wherein R stands for hydrogen and acetyl or of acid addition salts thereof in which a corresponding compound of general formula II ##STR2## in which R has the same meaning as above is reacted with 2-(dimethylamino)-ethyl chloride in a biphasic system of water and a non-combustible aliphatic polychlorinated hydrocarbon solvent in the presence of calcium hydroxide or of barium hydroxide. The process is advantageously performed at a temperature between 15.degree. and the refluxing temperature of the aliphatic polychlorinated hydrocarbon solvent. The process is optionally performed in the presence of a suitable quaternary ammonium halide. In the process the amount of calcium hydroxide or barium hydroxide is advantageously 1-3 moles per 1 mole of the compound of general formula II, the amount of aliphatic polychlorinated hydrocarbon solvent is advantageously 15-40 ml and that of water 3-10 ml per g of the compound of general formula II and the ratio aliphatic chlorinated hydrocarbon solvent:water is advantageously 2:1 to 10:1.
    • 本发明涉及制备通式I的苯并硫氮杂衍生物的方法,其中R代表氢和乙酰基或其酸加成盐,其中相应的通式II的化合物,其中R具有 在氢氧化钙或氢氧化钡存在下,在水和不燃性脂族多氯代烃溶剂的双相体系中,与上述相同的含义与2-(二甲基氨基) - 乙基氯反应。 该方法有利地在15℃和脂族多氯代烃溶剂的回流温度之间进行。 该方法任选地在合适的季铵卤化物存在下进行。 在该方法中,氢氧化钙或氢氧化钡的量相对于每1摩尔通式II的化合物有利地为1-3摩尔,脂族多氯代烃溶剂的量有利地为15-40毫升,水的量为3-10毫升 g的通式II化合物和脂族氯代烃溶剂:水的比例有利地为2:1至10:1。