反式-(1R,2S)-2-(3,4-二氟苯基)-1-氨基环丙烷的合成工艺改进

Process Improvement on the Synthesis of Trans-(1R,2S)-2-( 3,4-difluorophenyl)-1-amino Trimethylene

以3,4-二氟苯甲醛为起始原料,依次经缩合、酰卤化、酯化、不对称环丙烷化和霍夫曼降解反应制得中间体——反式-2-(3,4-二氟苯基)-1-氨基环丙烷[(±)-7];(±)-7与D-扁桃酸成盐后再水解合成了替格瑞洛关键中间体——反式-(1R,2S)-2-(3,4-二氟苯基)-1-氨基环丙烷,总收率24%,其结构经1H NMR和ESI-MS确证。

A intermediate, trans-2-（ 3,4-difluorophenyl ） -1-amino trimethylene [ （ ＋ ） -7 ], was prepared by condensation, acylation, esterification, asymmetric cyclopropanation and Hofmann degradation, using 3,4-difluorobenzaldehyde as the starting material. A key intermediate of Ticagrelor, trans- （1R,2S）-2-（3,4-difluorophenyl）-1-amino trimethylene, was synthesized in total yield of 24% by salifinstion of （ ＋ ）-7 with （R）-（ - ）-mandelic acid and then hydrolyzing. The structure was confirmed by ＇H NMR and ESI-MS.