反应 #46345

反应方程式

(RS)-2-{1-[Bis(4-chlorophenyl)methyl]-azetidin-3-yl}-2-(3,5-difluorophenyl)-N-propylacetamide

methylamine

1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride

hydroxybenzotriazole hydrate

(RS)-{1-[bis(4-chlorophenyl)-methyl]azetidin-3-yl}-(3,5-difluorophenyl)acetic acid hydrochloride

→

(RS)-2-{1-(bis(4-chlorophenyl)methyl]azetidin-3-yl}-2-(3,5-difluorophenyl)-N-methylacetamide

溶剂

tetrahydrofuran

dichloromethane

triethylamine

反应条件

后处理

1. 1
   其他The solution obtained
2. 2
   workup.ADDITIONfilled with 3 g of fine silica (0.040-0.063 mm)
3. 3
   洗涤eluted with dichloromethane with the aid of a Duramat pump
4. 4
   workup.ADDITIONThe fractions containing only the desired product
5. 5
   浓缩concentrated to dryness under reduced pressure (2.7 kPa) at 40° C

实验过程

(RS)-2-{1-[Bis(4-chlorophenyl)methyl]-azetidin-3-yl}-2-(3,5-difluorophenyl)-N-propylacetamide may be prepared in the following manner: 0.050 cm3 of a 2 M solution of methylamine in tetrahydrofuran, 29 mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, 0.028 cm3 of triethylamine and 1.5 mg of hydroxybenzotriazole hydrate are successively added to a solution of 50 mg of (RS)-{1-[bis(4-chlorophenyl)-methyl]azetidin-3-yl}-(3,5-difluorophenyl)acetic acid hydrochloride in 2 cm3 of anhydrous dichloromethane, at a temperature in the region of 20° C. The solution obtained is stirred at a temperature in the region of 20° C. for about 12 hours. The reaction medium is deposited on a Varian cartridge (6 cm3) filled with 3 g of fine silica (0.040-0.063 mm) conditioned and eluted with dichloromethane with the aid of a Duramat pump. The fractions containing only the desired product are combined and concentrated to dryness under reduced pressure (2.7 kPa) at 40° C. 19 mg of (RS)-2-{1-(bis(4-chlorophenyl)methyl]azetidin-3-yl}-2-(3,5-difluorophenyl)-N-methylacetamide are thus obtained in the form of a white solid (1H NMR spectrum (300 MHz, CDCl3, δ in ppm): 2.66 (mt: 1H); 2.76 (d, J=5 Hz: 3H); 2.93 (mt: 1H); 3.10 (mt: 2H); 3.44 (broad t, J=7.5 Hz: 1H); 3.59 (d, J=10.5 Hz: 1H); 4.28 (s: 1H); 5.41 (unresolved complex: 1H); 6.71 (tt, J=9 and 2.5 Hz: 1H); 6.83 (mt: 2H); from 7.20 to 7.35 (mt: 8H)].

来源