目的改进瑞格列净(remogliflozin)的合成方法。方法以4-异氧丙基苯甲醛为原料,经还原、溴代、C-烃化、水合肼环合、羟基磺酰化保护、N-烷基化、缩合脱保护等7步反应得到中间体1-异丙基-3-羟基-4-(4-异丙氧基苄基)-5-甲基-1H-吡唑(9);以五乙酰-β-D-葡萄糖为原料,经溴代得到1-溴代四乙酰-β-D-葡萄糖(11);中间体9与11经O-烃化缩合及脱保护基反应得到目标产物瑞格列净,其结构经MS、IR、1H-NM R及13C-NM R确证。结果与结论该合成路线总收率为37.4%(以4-异氧丙基苯甲醛计),较文献收率提高了2.9%,纯度大于99.3%,新工艺路线原料廉价易得、反应条件温和、后处理简单,适于工业化生产。 Objective To improve the synthesis of remogliflozin. Methods 4-isooxypropylbenzaldehyde was used as the starting material to obtain the intermediate reaction through reduction, bromination, C-alkylation, hydrazine hydration, hydroxysulfonylation protection, N-alkylation and condensation deprotection Isopropyl-3-hydroxy-4- (4-isopropoxybenzyl) -5-methyl-1H-pyrazole (9) Bromo-4-acetyl-β-D-glucose (11). The intermediates 9 and 11 were reacted with O-alkylation and deprotection to obtain the target product regurgitant. The structure was confirmed by MS, IR, 1H-NM R and 13C-NM R. RESULTS AND CONCLUSION The overall yield of the synthetic route was 37.4% (based on 4-isooxypropyl benzaldehyde), which was 2.9% higher than that of the literature and the purity was more than 99.3%. The raw materials of the new route were cheap and easily available, and the reaction conditions were mild , Post-processing simple, suitable for industrial production.