降糖药达格列净中2种杂质的合成

Synthesis of Two Impurities in Dapagliflozin

为定量控制降糖药达格列净中的杂质,对达格列净中的2个杂质5-溴-2-氯-2′-乙氧基二苯甲酮(1)和5-溴-2-氯-2′-乙氧基二苯甲烷(2)进行了定向合成,以5-溴-2-氯苯甲酸和苯酚经缩合、Fries重排,然后乙基化得到杂质1,杂质1再经还原得到杂质2。其结构经核磁共振氢谱和质谱确证结构。

To perform the quality control of dapagliflozin, two impurities of dapagliflozin including 5-bromo-2-chlorophenyl-2′-ethoxyldiphenylmethanone（1） and 5-bromo-2-chloro-2′-ethoxyl diphenylmethane（2） were synthesized. Impurity 1 was prepared via condensation, Fries rearrangement and ethylation using 5-bromo-2-chlorobenzoic acid and phenol as the starting materials. Impurity 2 was obtained from reduction of impurity 1.The structures of Impurity 1 and Impurity 2 were characterized using1 H NMR and MS.