1,2-Dichloroethane → 4-(2-chloro-5-fluoropyrimidin-4-yl)-N-[1-(3-chlorophenyl)-2-hydroxyethyl]-benzamide

Participants

Reaction Steps

To a solution of 4-(2-chloro-5-fluoropyrimidin-4-yl)-benzoic acid methyl ester (0.3 g, 1.13 mmol) in 4 mL of THF was added a solution of LiOH (0.378 g, 9.0 mmol) in 4 mL of H2O and stirred at room temperature for 3 hours. The reaction mixture was extracted with ethyl acetate (10 mL) to remove any byproduct. The aqueous layer was acidified to pH=3 with 6N HCl and the resulting precipitate filtered. To a suspension of these solids in 5 mL of DMF was added EDC (0.26 g, 1.36 mmol), HOBt (0.229 g, 1.70 mmol), and Et3N (0.236 mL, 1.70 mmol) and stirred for 10 minutes. (S)-(+)-3-chlorophenyl glycinol (0.353 g, 1.70 mmol) was added and the reaction stirred overnight. After 18 hours, the reaction was diluted with ethyl acetate and washed with 1N HCl, NaHCO3, saturated NaCl. The organic layer was concentrated and the residue purified by chromatography (Silica, 40% ethyl acetate in hexanes) to afford 4-(2-chloro-5-fluoropyrimidin-4-yl)-N-[1-(3-chlorophenyl)-2-hydroxyethyl]-benzamide (0.15 g, 55%) as a white solid. 1H NMR (CDCl3, 500 MHz): 8.40 (d, 1H), 8.15 (d, 2H), 7.90-7.95 (m, 2H), 7.32 (s, 1H), 7.22-7.29 (m, 2H), 7.05-7.08 (m, 1H), 5.18-5.22 (m, 1H), 3.95-4.00 (m, 2H), 1.80 (s, 2H). LCMS: ES+=406.

Provenance & Evidence