Sodium Hydroxide → 6-(3-Fluoropropoxy)-3-pyridinecarboxylic acid

Participants

Reaction Steps

Sodium hydride (0.220 g, 5.50 mmol) was added to a solution of 3-fluoropropan-1-ol (0.390 g, 5 mmol) in N,N-dimethylformamide (5 mL). The mixture was stirred under an atmosphere of nitrogen for 25 min and added a solution of ethyl 6-chloronicotinate (0.928 g, 5.00 mmol) in N,N-dimethylformamide (2.5 mL). The reaction mixture was stirred for 35 min and then quenched with water. The reaction mixture was extracted with ethyl acetate, the organic layer was washed with brine, dried over magnesium sulfate and evaporated in vacuo. Purification by column chromatography using a gradient of ethyl acetate in heptane yielded an oil. The crude was dissolved in 1M sodium hydroxide, (16.50 mL, 16.50 mmol) and ethanol (20 mL) and heated to 50° C. for 1.5 h. The organic solvent was removed in vacuo, and the residual aqueous solution was cooled on ice. 2 M hydrochloric acid was added until an acidic pH was reached. The obtained precipitate was filtered off, washed with ice-water, and dried in vacuo affording the title compound, 0.53 g (81%) as a white solid; 1H NMR (400 MHz, DMSO-d6) δ ppm 8.71 (dd, 1 H), 8.14 (dd, 1 H), 6.90 (dd, 1 H), 4.65 (t, 1 H), 4.54 (t, 1 H), 4.43 (t, 2 H), 2.05-2.19 (m, 2 H); MS (APPI/APCI) m/z 228[M+H+].

Provenance & Evidence