Ammonia → (5-Fluoropyridin-2-yl)methanamine

Participants

Reaction Steps

Combine a mixture of 2-cyano-5-fluoropyridine (63.2 g, 0.52 mol), 22.5 g of Raney nickel, and ethanol (1.5 L) saturated with ammonia and hydrogenate at 500 p.s.i. and 70° C. for 16 h. Chromatograph the dark purple liquid over flash silica gel (methylene chloride/methanol/ammonia hydroxide—95:4.5:0.5) to give, after concentration at 25-30° C., a yellow liquid of the pure desired free base, 25.0 g (44%); 1H NMR (DMSO-d6) δ 8.43 (d, J=2.9 Hz, 1H), 7.66 (m, 1H), 7.50 (m, 1H), 3.77 (s, 2H), 2.10 (br, 2H); MS (ESI) m/z 127 (m+H). Add to a solution of the free base (20.0 g, 159.0 mmol) in 150 ml of 1,4-dioxane, 4N HCl in dioxane (150 mL, 3.8 eq.) and a white solid separates immediately. Dilute the solid with ethyl ether (300 mL) and filter. Dry the product at 20 mm Hg, 60° C., to give the pure dihydrochloride title compound, 30.0 g (95%); 1H NMR (DMSO-d6) δ 8.61 (d, J=2.9 Hz, 1H), 8.50 (brs, 3H), 7.82 (m, 1H), 7.62 (m, 1H), 7.50 (br, 1H), 4.18 (m, 2H); MS (ESI) m/z 127 (m+H, free base).

Provenance & Evidence