论文部分内容阅读
以D-扁桃酸(9)为原料,与对硝基苯乙胺盐酸盐(2)经酰化、还原、Boc保护、催化氢化得到(R)-N-(2-羟基-2-苯乙基)-N-[2-(4-氨基苯基)乙基]氨基甲酸叔丁酯(6),硫脲与4-氯乙酰乙酸乙酯经环合、酯水解得到2-氨基噻唑-4-乙酸(7),中间体6与中间体7缩合,最后脱氨基保护基得到米拉贝隆(1),总收率为20.9%,所得产品经MS和~1H NMR确证结构。该路线反应条件温和,操作简单,原料成本低廉,适合工业化生产。
D-mandelic acid (9) was used as the starting material to react with p-nitrophenethylamine hydrochloride (2) via acylation, reduction, Boc protection and catalytic hydrogenation to obtain (R) -N- Ethyl) -N- [2- (4-aminophenyl) ethyl] carbamate (6). Thiourea and ethyl 4-chloroacetoacetate were cyclized to give 2-aminothiazole- 4-acetic acid (7). Intermediate 6 was condensed with intermediate 7. The final deaminated protecting group gave mirabelone (1) in a total yield of 20.9%. The product was confirmed by MS and 1H NMR. The route has mild reaction conditions, simple operation, low raw material cost and suitable for industrialized production.