(6-BROMO-PYRIDIN-3-YL)-METHANOL

Uses

2-Bromo-5-pyridinemethanol is used as a pharmaceutical intermediate.

Synthesis

General procedure for the synthesis of 2-bromo-5-(hydroxymethyl)pyridine from 2-bromo-5-formylpyridine: Sodium borohydride (4.88 g, 0.026 mol) was added batchwise to a solution of 6-bromonicotinaldehyde (20.0 g, 0.11 mol) in methanol (108 mL) at 20-30 °C. The reaction mixture was stirred at room temperature for 2 hours. Subsequently, the reaction mixture was diluted with saturated aqueous ammonium chloride solution. The mixture was concentrated to remove methanol and the resulting aqueous solution was extracted with ethyl acetate. The organic phase was washed sequentially with saturated aqueous sodium bicarbonate and brine, dried over magnesium sulfate, filtered and concentrated to afford 2-bromo-5-(hydroxymethyl)pyridine (18.61 g, 92% yield) as a light yellow solid.1H-NMR (300 MHz, CDCl3) δ (ppm): 8.36 (d, J = 2.7Hz, 1H), 7.60 (dd, J = 8.1, 2.7Hz, 1H). 2.7 Hz, 1H), 7.49 (d, J = 8.1 Hz, 1H), 4.72 (s, 2H), 1.95 (s, 1H).

References

[1] Patent: WO2013/44360, 2013, A1. Location in patent: Paragraph 000299-000300
[2] Patent: WO2006/114213, 2006, A1. Location in patent: Page/Page column 29-30
[3] Patent: WO2012/177603, 2012, A2. Location in patent: Page/Page column 105-108
[4] Journal of Organic Chemistry, 2004, vol. 69, # 2, p. 250 - 262
[5] Dalton Transactions, 2012, vol. 41, # 3, p. 1074 - 1081