Dimethylformamide → HCID 22473215, compound

Participants

Reaction Conditions

Reaction Steps

A solution of BuLi (3.0 mmol) in hexanes (1.6 M, 1.87 ml) was added to a stirred solution of 2-bromo-5-(1-methylpyrrolidin-2-yl)pyridine (480 mg, 2.0 mmol) in THF (50 ml) at −78° C. under N2. The reaction was stirred at −78° C. for 10 min, DMF (462 μl, 6.0 mmol) was added and the reaction allowed to warm slowly to room temperature and stirred at room temperature for a further 1 h. MeOH (50 ml) was added, followed by sodium borohydride (75 mg, 2.0 mmol) and then the reaction mixture was stirred at room temperature for 1 h. NH4Cl solution (10 ml) was added cautiously. The resulting mixture was concentrated under reduced pressure, then dissolved in MeOH/CH2Cl2 (1:1, 50 ml) and dry loaded onto silica. The crude residue was purified by column chromatography on silica using 5% MeOH/CH2Cl2 containing 1% NH3 to yield the desired hydroxymethylpyridine (100 mg, 26%). 1H NMR (400 MHz, CDCl3) δ 8.46 (1H, d, J=2.0 Hz), 7.70 (1H, dd, J=8.0, 2.0 Hz), 7.25 (1H, d, J=8.0 Hz), 4.75 (2H, s), 4.18 (1H, broad s), 3.28-3.18 (1H, m), 3.09 (1H, J=8.3 Hz), 2.31 (1H, q, J=9.0 Hz), 2.22-2.16 (1H, m), 2.16 (3H, s), 2.05-1.65 (3H, m). m/z (ES+) 193 (M+H+).

Provenance & Evidence