1,2-Dichloroethane → 2-[4-(1-hydroxy-1-methylethyl)phenyl]-N-{(1R)-1-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethyl}acetamide

Participants

Reaction Steps

To a suspension of [4-(1-hydroxy-1methylethyl)phenyl]acetic acid (266 mg, 1.37 mmol), (1R)-1-(5-(2,2,2-trifluoroethoxy)pyridin-2-yl)ethylamine bis-hydrochloride (400 mg, 1.37 mmol), EDC (315 mg, 1.64 mmol), and 1-hydroxy-7-azabenzotriazole (224 mg, 1.64 mmol) in DMF (20 mL) was added N,N-diisopropylethylamine (741 uL, 4.25 mmol). The reaction mixture was stirred at room temperature overnight, then concentrated to ˜5 mL and diluted with CH2Cl2 (50 mL). The solution was washed with water (50 mL) and the aqueous layer was extracted with CH2Cl2 (2×30 mL). The combined organic layer was washed with water (50 mL), dried over MgSO4, concentrated and purified by normal phase chromatography (15-100% EtOAc/Hexanes) to give 270 mg (50%) of 2-[4-(1-hydroxy-1-methylethyl)phenyl]-N-{(1R)-1-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethyl}acetamide as a white solid. 1H NMR (CDCl3, 400 MHz) 8.20 (d, J=2.75 Hz, 1H), 7.45 (m, 2H), 7.22 (m, 4H), 6.68 (d, J=7.33 Hz, 1H), 5.11 (quint. J=6.96 Hz, 1H), 4.38 (q, J=8.00 Hz, 2H), 3.57(s, 2H), 1.59 (s, 6H), 1.40 (d, J=6.77 Hz, 3H); MS (Electrospray): m/z 397.3 (M+H).

Provenance & Evidence