A mixture of 133 mg (0.40 mmol) of (3R)-3-[(1,1-dimethylethoxycarbonyl)amino]-4-(2,4,5-trifluorophenyl)butanoic acid and 162 mg (0.50 mmol) of 8-benzyl-2-(trifluoromethyl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine, hydrochloride in 1.5 mL of acetonitrile at 0° C. was treated sequentially with 81 mg (0.42 mmol) of EDC and 0.047 mL (0.42 mmol) of N-methyl morpholine. After 10 min, the mixture was warmed to ambient temperature and stirred for 3 h, then partitioned between 10 mL of ethyl acetate and 4 mL of water. The organic layer was washed sequentially with saturated aqueous sodium bicarbonate solution and brine, dried and concentrated to give 281 mg of the title compound as a mixture of diastereomers. Purification by flash chromatography (silica gel, 10 to 35% ethyl acetate/hexane) followed by HPLC on a Chiralpak AD column (9% ethanol/hexane) gave 51 mg of the faster eluting isomer and 47 mg of the slower eluting isomer.
