那格列奈的绿色合成与质量分析

Synthetic study and quality analysis of nateglinide

以4-异丙基苯甲酸为起始原料，经催化氢化、酰氯化，再与D-苯丙氨酸甲酯反应得酯化物，在25～30℃搅拌水解10h后，调pH=1，用V（甲醇）：V（水）=4：1]100mL重结晶，用H-型晶种低温粉碎得到微粒晶种，在中温加入晶种引导结晶，质量收率达72％。产品结构经IR与1HNMR表征，产品晶型经X-射线衍射为H-型晶体。水分含量符合药用标准。

4-Isopropyl-benzoic acid taken as starting material was processed through catalytic hydrogenation, acylchloriration and reaction with D-phenylalanine-methyl, producing esterified outputs which will be recrystallized with [ V（methanol） ： V（H2O） = 4 ： 1 ] 100 mL when the adjusted pH value equals 1, after 10 h hydrolyzation in 25 -30℃ water churning. Crystallization will be inducted by adding the particulate seed crystal which can be acquired through macrothermolly crushing H-form crystalline seed, and the yield will reach 72%. The product structure is characterized by IR and 1H NMR and the crystalline modification is H-form crystal in X-rays diffraction analysis and moisture content meets pharmaceutical criteria.