Cyclohexanemethylamine → (RS)-2-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-2-(3,5-difluoro-phenyl)-N-cyclohexylmethylacetamide

Participants

Reaction Conditions

Reaction Steps

(RS)-2-{1-[Bis(4-chlorophenyl)methyl]-azetidin-3-yl}-2-(3,5-difluorophenyl)-N-cyclohexyl-methylacetamide may be prepared in the following manner: 0.016 cm3 of aminomethylcyclohexane, 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 {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 then eluted with dichloromethane with the aid of a Duramat pump, collecting 2-cm3 fractions. Fractions 2 to 3 are combined and concentrated to dryness under reduced pressure (2.7 kPa) at 40° C. 49 mg of (RS)-2-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-2-(3,5-difluoro-phenyl)-N-cyclohexylmethylacetamide are thus obtained in the form of a white foam [1H NMR spectrum (300 MHz, CDCl3, δ in ppm): from 0.75 to 1.75 (mt: 11H); 2.65 (mt: 1H); from 2.85 to 3.15 (mt: 5H); 3.42 (broad t, J=7.5 Hz: 1H); 3.57 (d, J=10.5 Hz: 1H); 4.27 (s: 1H); 5.40 (mt: 1H); 6.71 (broad t, J=9 Hz: 1H); 6.83 (mt: 2H); from 7.15 to 7.40 (mt: 8H)].

Provenance & Evidence