1218935-59-1
1218935-59-1 结构式
基本信息
-2-(2,5-二氟苯基)吡咯烷
(R)-2-(2,5-二氟苯基)吡咯烷
(2R)-2-(2,5-二氟苯基)吡咯烷
2-(2,5-二氟苯基)吡咯烷 拉罗替尼中间体
(2R)-2-(2,5-二氟苯基)吡咯烷盐酸盐
Larotrectinib Pyrrolidine Impurity
(2R)-2-(2,5-DIFLUOROPHENYL)PYRROLIDINE
(2R)-2-(2,5-DIFLUOROPHENYL)PYRROLIDINE-HCL
Pyrrolidine, 2-(2,5-difluorophenyl)-, (2R)-
(2R)-2-(2,5-Difluorophenyl)pyrrolidine hydrochloride
Larotrectinib Impurity 7(Larotrectinib Pyrrolidine Impurity)
物理化学性质
制备方法
1443538-31-5
1218935-59-1
一般步骤:向(R)-1-((S)-叔丁基亚磺酰基)-2-(2,5-二氟苯基)吡咯烷(8.60 g,29.9 mmol)的甲醇(60 mL)溶液中,在0℃下缓慢加入4M盐酸的二恶烷溶液(37.4 mL,150 mmol)。反应混合物在室温下搅拌12小时。反应完成后,将混合物在真空下浓缩,残余物溶于水(100 mL)中,并用乙酸乙酯(100 mL)洗涤。分离水层,用1N氢氧化钠水溶液(150 mL)中和,随后用二氯甲烷(100 mL × 3)萃取。合并有机层,用饱和盐水洗涤,无水硫酸钠干燥,过滤并真空浓缩,得到(R)-2-(2,5-二氟苯基)吡咯烷(5.06 g,收率92%),为微红色油状物。1H-NMR(CDCl3,Varian,400 MHz):δ 1.56-1.65(1H,m),1.78-1.93(3H,m),2.21-2.30(1H,m),3.01-3.08(1H,m),3.13-3.18(1H,m),4.39(1H,t,J = 7.6 Hz),6.82-6.88(1H,m),6.91-6.97(1H,m),7.22-7.26(1H,m)。
参考文献:
[1] Patent: CN107286070, 2017, A. Location in patent: Paragraph 0079; 0080; 0081
[2] Patent: US2016/168156, 2016, A1. Location in patent: Paragraph 0207; 0215; 0216
[3] Patent: CN109053525, 2018, A. Location in patent: Paragraph 0021; 0031; 0032; 0033
[4] Patent: CN108003161, 2018, A. Location in patent: Paragraph 0324; 0325; 0345-0347