tert-Butanol → 2-Amino-4-Methoxypyridine

Participants

Reaction Conditions

Reaction Steps

To a cooled (0° C.) suspension of 4-methoxypyridine-2-carboxylic acid hydrazide (10.0 g, 59.9 mmol) and trifluoroacetic acid (6.83 g, 59.9 mmol) in tetrahydrofuran (120 ml) was added tert-butylnitrite (18.52 g, 179.6 mmol) at such a rate to keep the internal temperature below 5° C. (ca. 45 min). Once addition was complete the mixture was allowed to stir at 0° C. for 30 min and then the solvent was removed in vacuo. Toluene (100 ml) was added and the mixture heated under reflux for 1 h before adding tert-butanol (15 ml, 155.7 mmol). After heating at reflux for a further 10 h the reaction was cooled and the solvent evaporated in vacuo. The residue was suspended in toluene (100 ml), trifluoroacetic acid (5 ml) was added and the mixture heated at reflux for 5 h. The solvent was removed on a rotary evaporator and the residue purified by flash column chromatography on silica eluting with dichloromethane/methanol/conc. ammonia (97:3:0.3) to furnish 4-methoxypyridin-2-ylamine (4.50 g, 61%) as a pale brown solid. 1H NMR (400 MHz, CDCl3) δH 3.90 (3H, s), 6.12 (1H, s), 6.32 (1H, d, J 7), 7.52 (1H, d, J 7), 7.75 (1H, br s).

Provenance & Evidence