中文摘要：

目的优化达格列净的合成工艺。方法以5-溴-2-氯苯甲酸为原料，经酰化、傅克反应、还原得到关键中间体5-溴-2-氯4′-甲氧基二苯甲烷，该中间体与2，3，4，6-四-O-三甲基硅烷基-D-吡喃葡萄糖酸-1，5-内酯经缩合、醚化、脱甲氧基、酯化、脱保护得到目标化合物达格列净。结果与结论达格列净的总收率为26．4％（以5-溴-2-氯4’-甲氧基二苯甲烷计），其结构经^1H—NMR、^13C—NMR、MS谱确证。在2-氯-5-（1-甲氧基-D-吡喃葡萄糖-1-基）-4’-甲氧基二苯甲烷的合成中，采用混合溶剂甲苯-四氢呋喃（体积比3．5：1）减少了副产物三甲硅烷基糖苷的生成；在2-氯-5-（吡喃葡萄糖-1-基）-4＇-甲氧基二苯甲烷的合成中，在反应溶剂中加入适量水，提高了生成β构型糖苷的选择性，且用正己烷除去极性小的杂质，避免多次乙醇重结晶，使目标物的总收率提高至26．4％。

英文摘要：

Dapagliflozin, a novel selective sodium-glucose co-transporter type Ⅱ （SGLT2） inhibitor, is developed by the cooperation of AstraZeneca（ $ AZN） and Bristol-Myers Squibb（ $ BMY）. Using 5-bromo- 2-chlorobenzoic acid and D-glucono-1,5-lactone as the starting materials, dapagliflozin was synthesized via eight steps reactions. Its total yield was 26. 4% [ according to the quantity of intermediate 7,4-bromo-1-chloro-2-（4-ethoxybenzyl）benzene] and the HPLC purity of the final product was 99.4%. The structures of dapagliflozin and some important intermediates were confirmed by ^1H-NMR, ^13C-NMR and MS. In the synthesis of intermediate 8,2-chloro-5-（ 1-methoxy-D-glucopyranose-1-yl ）-4＇-ethoxydiphenyl, various mixed solvents were investigated and eventually the mixed solvent-toluene-THF （ V： V = 3.5： 1 ） -got the highest yield. Intermediate 9,2-ehloro-5-（ D-glucopyranose-l-yl ）-4＇-ethoxydiphenyl, was highly yielded when the ratio of intermediate 8 and the amount of water was 1： 1 （ n： n）. During the purification of intermediate 9, nhexane was used to remove small polar impurities, which reduced the amount of solvent and the times of recrystallization.