Dimethylformamide → HCID 59770928, compound

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of 2,6-dibromopyridine (3 g, 12.7 mmol) in a mixture of THF (8 mL), ether (16 mL), and hexane (8 mL) was added n-BuLi (7.94 mL, 12.7 mmol, 1.6 M in hexane) drop-by-drop at −78° C. over 5 min. After the mixture was stirred for 5 min, DMF (2.01 mL, 26.3 mmol) was slowly added dropwise to the mixture over 10 min at the same temperature. The reaction mixture was warmed to −50° C. and quenched with MeOH (15 mL). Then, NaBH4 (487 mg, 12.9 mmol) was added at room temperature. After addition of acetone (1.5 mL), the mixture was diluted with EtOAc (300 mL). The whole was washed with water (6 mL×3) and brine (6 mL) and dried over MgSO4. Solvent was evaporated and the residue was purified by column chromatography on silica gel eluted with 20% EtOAc in hexane to give 380 mg (13%) of 2-Bromo-6-(methylaminomethylcarbonyl)pyridine and 1.11 g (46%) of the oil 2-bromo-6-hydroxymethylpyridine. Bromo-6-(methylaminomethylcarbonyl)pyridine: 1H NMR (CDCl3) δ 7.53 (m, 1H, H-4), 7.38 (d, 1H, J=7.9 Hz), 7.28 (d, 1H, J=7.5 Hz), 5.14 (s, 2H, CH2), 2.12 (s,3H, Me); 13C NMR (CDCl3) δ 170.9 (CO), 157.7 (C-6), 142.1 (C-2), 139.5 (C-4), 127.7 (C-3), 120.9 (C-5), 66.4 (CH2), 21.3 (Me). Mass spectrum (ES+): m/e 230 (M++1). 2-bromo-6-hydroxymethylpyridine: 1H NMR (CDCl3) δ 7.56 (t, 1H, J=7.7 Hz), 7.46 (d, 1H, J=7.7 Hz), 7.37 (d, 1H, J=7.7 Hz), 4.85 (s, 2H, CH2); 13C NMR (CDCl3) δ 162.0 (C-6), 141.7 (C-2), 139.6 (C-4), 124.8 (C-3), 119.8 (C-5), 64.6 (CH2).

Provenance & Evidence