4-Methylmorpholine → (+/-)-3-{4-[2-Cyclohexyl-1-(4'-trifluoromethyl-biphenyl-4-yl)-ethoxy]-3-methyl-benzoylamino}-2-methyl-propionic acid ethyl ester

Participants

Reaction Steps

A solution of (±)-4-[2-cyclohexyl-1-(4′-trifluoromethyl-biphenyl-4-yl)-ethoxy]-benzoic acid (0.0813 g, 0.174 mmol) in THF (1.7 mL) is treated with 2-chloro-4,6-dimethoxy-[1,3,5]triazine (CDMT, 0.0338 g, 0.193 mmol) and N-methyl morpholine (NMM, 0.020 mL, 0.27 mmol). The mixture is added to a flask containing (±)-3-amino-2-hydroxy-propionic acid ethyl ester (0.0465 g, 0.274 mmol). Additional NMM (0.030 mL, 0.273 mmol) and H2O (0.4 mL) are added and the reaction is stirred overnight. The reaction mixture is dissolved in EtOAc (10 mL) and washed with 0.1 N HCl (2×10 mL), ph=7 phosphate buffer (1×), brine (1×), dried over MgSO4, filtered, and conc. The residue is loaded onto silica gel and eluted with hexanes using a gradient of 10% EtOAc to 60% EtOAc giving (±)-3-{4-[2-cyclohexyl-1-(4′-trifluoromethyl-biphenyl-4-yl)-ethoxy]-3-methyl-benzoylamino}-2-methyl-propionic acid ethyl ester (0.0568 g, 56%) as a white foam. MS (ES): 582.3 [M−H]−.

Provenance & Evidence