Dimethylformamide → HCID 59770928, compound

Temperature

-50 °C

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).

1. customquenched with MeOH (15 mL)
2. washThe whole was washed with water (6 mL×3) and brine (6 mL)
3. dry with materialdried over MgSO4
4. customSolvent was evaporated
5. customthe residue was purified by column chromatography on silica gel
6. washeluted with 20% EtOAc in hexane

ORD record

ord-098fb303f5b84706ad6451523e811adc

Source dataset

uspto-grants-2008_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07414036B2