【摘要】 目的合成四氢苯并噻唑类抗肿瘤药物的关键中间体5-苯基异噁唑-3-羧酸乙酯(E)。方法以1-(3-氯-2,4,6-三羟基苯基)乙酮(A)为起始原料,采用溴化苄保护三个酚羟基,随后在Na H作用下与草酸二乙酯缩合得到中间体C; C与盐酸羟胺环合得到异噁唑(D),最后在BCl3作用下脱除苄基保护基得到目标产物(E)。结果四步反应总收率为23. 1%,且目标产物和所有中间体的结构均经~1H NMR、ESI-MS进行确证。结论此方法具有原料简易可得、操作步骤简单、收率较高的特点,适合在多个酚羟基存在条件下合成异噁唑类衍生物。更多还原

【Abstract】 Objective: To synthesize ethyl 5-phenylisoxazole-3-carboxylate( E),a key intermediate of an antitumor drug bearing tetrahydrobenzothiazole structure. Methods: Starting from 1-( 3-chloro-2,4,6-trihydroxyphenyl) ethan-1-one( A),the intermediate( C) was obtained by protection of the three hydroxyl groups with benzyl bromide,followed by condensation with diethyl oxalate in the presence of Na H; C was cyclized with hydroxylamine hydrochloride to deliver isoxazole( D),which was then deprotection by BCl3 to generate the target product( E). Results: A total yield of 23. 1% was obtained,and the structures of the target compound and three intermediates were elucidated by ~1H NMR and ESI-MS. Conclusion: This method features readily available materials,simple operation and high yields,which is suitable for the preparation of isoxazole derivatives in the presence of multi-hydroxyl groups.更多还原