Hydrochloric Acid → (E)-1-[3-cyclohexyl-2-(4-methanesulfonyl-3-trifluoromethyl-phenyl)-acryloyl]-3-methyl-urea

Participants

Reaction Conditions

Reaction Steps

A solution of (E)-3-cyclohexyl-2-(4-(methanesulfonyl)-3-(trifluoromethyl)-phenyl)-acrylic acid (282 mg, 0.75 mmol) in fluorobenzene (1 mL) and N,N-dimethylformamide (3 μL) at 25° C. was treated dropwise with oxalyl chloride (81 μL, 0.9 mmol) over 2-3 min. The clear solution was stirred at 25° C. for 1 h and then treated with methyl urea (167 mg, 2.25 mmol). The resulting suspension was heated at 70° C. (bath temperature) for 10 min and then treated with pyridine (121 μL, 1.5 mmol). The reaction mixture was then stirred at 70° C. for 20 h. The reaction mixture was then cooled to 25° C. and diluted with ethyl acetate (50 mL) and a 3N aqueous hydrochloric acid solution (40 mL). The two layers were separated, and the aqueous layer was extracted with ethyl acetate (1×20 mL). The combined organic extracts were successively washed with a saturated aqueous sodium bicarbonate solution (1×50 mL) and a saturated aqueous sodium chloride solution (1×50 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40M, Silica, 4/1 hexanes/ethyl acetate) afforded the (E)-1-[3-cyclohexyl-2-(4-methanesulfonyl-3-trifluoromethyl-phenyl)-acryloyl]-3-methyl-urea (104 mg, 32%) as a white solid: mp 199-202° C. EI-HRMS m/e calcd for C19H23F3N2O4S (M+) 432.1331, found 432.1332.

Provenance & Evidence