医药中间体伊索克酸的合成工艺改进

Improvement of Synthetic Process of Medical Intermediat Isoxepac

采用逆合成法确定以对羟基苯乙酸甲酯和苯酞为起始原料,在醇钠作用下,对羟基苯乙酸甲酯与苯酞在130℃发生亲核取代反应结束后加入一定量碱水控温水解,再以乙酸乙酯萃取有关杂质,水相用盐酸调节p H为2左右得中间体I,纯度97%以上;再以PPA和冰醋酸进行脱水环合反应得粗品,再经过乙酸乙酯精制得精品。通过此合成方法合成了高纯度的伊索克酸,总收率65. 5%,含量大于99%。

The method of reverse synthesis was used to determine methyl p-hydroxyphenylacetate and phenphthalein as starting materials.Under the action of sodium alcohol,a certain amount of alkaline water was added after the nucleophilic substitution reaction between methyl hydroxyphenylacetate and phenphthalein at 130 ℃ to control temperature and hydrolysis.The relevant impurities were then extracted by ethyl acetate,and intermediate I was obtained by regulated pH of about 2 with hydrochloric acid,with a purity of more than 97%.The crude product was obtained by dehydrating the ring reaction with PPA and glacial acetic acid,and then refined by ethyl acetate.The high purity issok acid was synthesized by this synthesis method.The total yield was 65.5% and the content was greater than 99%.