Ammonium Chloride → 2-(4-(2-(Trifluoromethyl)phenoxy)piperidin-1-yl)thiazole-5-carboxamide

Participants

Reaction Steps

To a solution of 2-{4-[2-(trifluoromethyl)phenoxy]piperidin-1-yl}-1,3-thiazole-5-carboxylic acid (14.5 g, 39 mmol), HOBt (5.3 g, 39 mmol)), HATU (23.7 g, 62 mmol) and NH4Cl (6.3 g, 117 mmol) in DMF (200 mL) at room temperature was added Hünig's base (34 mL, 195 mmol) over about 15 min. The mixture was stirred at room temperature overnight. After dilution with water, the mixture was extracted twice with EtOAc. The EtOAc extracts were combined, washed with 0.5 N NaOH (2×), diluted brine (1×), dried (Na2SO4) and concentrated. The residue was triturated with Et2O/hexanes (1:1) to give the title compound as a pale yellow solid. 1H NMR (500 MHz, acetone-d6): δ7.79 (s, 1H), 7.67-7.61 (m, 2H), 7.38 (d, 1H), 7.12 (t, 1H), 5.02 (s, 1H), 3.76 (t, 2H), 3.71-3.67 (m, 2H), 2.16 (t, 2H), 2.00-1.94 (m, 2H).

Provenance & Evidence