Trifluoroacetic acid → 4-[4-(4-Fluorophenyl)-1-piperidin-4-yl-1H-imidazol-5-yl]pyrimidine

Participants

Reaction Steps

TFA (242 mL) was added to a solution of tert-butyl 4-[4-(4-fluorophenyl)-5-pyrimidin-4-yl-1H-imidazol-1-yl]piperidine-1-carboxylate (C14) (30.70 g, 72.49 mmol) in dichloromethane (242 mL). After 18 hours, the reaction was treated with aqueous sodium hydroxide solution (2 N) until the pH of the mixture reached 12.0. {Caution: potential exotherm!} The aqueous layer was extracted with dichloromethane (2×500 mL), and the combined organic layers were concentrated in vacuo to provide the product as a yellowish solid. Yield: 23.90 g, 73.91 mmol, quantitative. 1H NMR (400 MHz, CDCl3) δ 1.82-1.92 (m, 2H), 2.14 (br d, J=12 Hz, 2H), 2.71 (ddd, J=12.3, 12.3, 2.2 Hz, 2H), 3.22 (br d, J=12 Hz, 2H), 4.82 (tt, J=12.0, 3.9 Hz, 1H), 7.03 (dd, J=8.8, 8.8 Hz, 2H), 7.16 (dd, J=5.3, 1.4 Hz, 1H), 7.41 (dd, J=8.9, 5.4 Hz, 2H), 7.83 (s, 1H), 8.57 (d, J=5.3 Hz, 1H), 9.30 (d, J=1.4 Hz, 1H).

Provenance & Evidence