Sodium Hydroxide → 8-Fluoro-10,11-dihydro-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-5-one

Participants

Reaction Steps

Combine crude 2-[2-(3-fluoro-phenyl)-ethyl]-nicotinic acid (2.06 g, 15.0 mmol) and polyphosphoric acid (100 g) and heat the mixture to 160° C. for 6 h. Allow slow cooling of the reaction mixture over 12 h, then reheat the mixture to 160° C. and pour it into ice (200 g). Complete the transfer using water and adjust the pH of the aqueous mixture to ˜8.0 with 50% aqueous sodium hydroxide solution. Extract the product with methylene chloride. Dry the combined organic extracts with magnesium sulfate, filter and concentrate. Purify the crude product via flash chromatography (25% ethyl acetate/hexanes to 50% ethyl acetate/hexanes) to provide 1.54 mg (81%) of purified product. LCMS (APCI-pos): 228.1 (M+H). 1HNMR (CDCl3, 400 MHz): δ8.63 (dd, 1H), 8.39 (dd, 1H), 8.01 (dd, 1H), 7.31 (dd, 1H), 7.02 (dt, 1H), 6.95 (dd, 1H), 3.46-3.43 (m, 2H), 3.23-3.21 (m, 2H). (Literature reference: Journal of Heterocyclic Chemistry 1971, 73).

Provenance & Evidence