Triethylamine → 2-{3-[2-(Trifluoromethyl)phenoxy]pyrrolidin-1-yl}-1,3-thiazole-5-carbonitrile

Participants

Reaction Steps

A suspension of 2-{3-[2-(trifluoromethyl)phenoxy]pyrrolidin-1-yl}-1,3-thiazole-5-carboxamide (670 mg, 1.9 mmol) and triethylamine (0.92 mL, 6.6 mmol) in CH2Cl2 (25 mL) was cooled with an ice-acetone bath. Triflic anhydride (412 μL, 2.4 mmol) was added dropwise over 10 min. The mixture was stirred for 5 min and then the cooling bath was removed. After further stirring at rt for 15 min, the mixture was quenched with water and extracted twice with CH2Cl2. The combined CH2Cl2 extracts were washed twice with diluted brine, dried (Na2SO4) and concentrated. Combi-Flash chromatography (40 g, 40-80% EtOAc in hexanes in 20 min, 35 mL/min, 18 mL/fraction) gave a gum that was triturated with hexanes-Et2O (1:1) to give the title compound as a white powder. 1H NMR (400 MHz, acetone-d6): δ 7.88 (s, 1 H), 7.67 (m, 2 H), 7.41 (d, 1 H), 7.18 (t, 1 H), 5.53 (s, 1 H), 3.99 (m, 1 H), 3.85-3.67 (m, 3 H), 2.63-2.45 (m, 2 H). MS (+ESI) m/z 340 (MH+).

Provenance & Evidence