Improved method for synthesis technology of n-hexadecyloxypropyl tenofovir disoproxil

The invention discloses an improved method for a synthesis technology of n-hexadecyloxypropyl tenofovir disoproxil, and belongs to the technical field of organic synthesis. The method comprises the following steps: 1, reacting n-hexadecyl bromide (2) with 1,3-propylene glycol (3) to obtain 3-n-hexadecyloxypropanol (4); 2, chlorinating PMPA (5) to obtain an acyl chloride intermediate (6); 3, esterifying the acyl chloride intermediate (6) and the 3-n-hexadecyloxypropanol (4) to obtain an intermediate (7); and 4, hydrolyzing and re-crystallizing the intermediate (7) to obtain the n-hexadecyloxypropyl tenofovir disoproxil (1), wherein the total yield is about 62%, and the purity is more than 99%. The method mainly has the advantages of easily available materials, simplicity in operation, low cost, and facilitation of industrial production. 本发明公开了种正十六烷氧丙基替诺福韦酯合成工艺的改进方法，属于有机合成的技术领域。本发明采用如下技术方案，包括以下步骤：①正十六烷基溴(2)和1，3-丙二醇(3)反应得3-正十六烷氧基丙醇(4)；②PMPA(5)经氯代得酰氯中间体(6)；③酰氯中间体(6)和3-正十六烷氧基丙醇(4)酯化得中间体(7)；④中间体(7)经水解、重结晶得正十六烷氧丙基替诺