2-Bromoethanol → 5-bromo-1-(2-hydroxyethyl)pyridin-2(1H)-one

Temperature

23 °C

To a stirring solution of 5-bromo-2(1H)-pyridone (1000 mg, 5.74 mmol) in dry DMF (10 mL) under nitrogen was added sodium hydride (60% dispersion in mineral oil, 264 mg, 11.5 mmol). After 20 min at 23° C., 2-bromoethyl alcohol (448 μl, 6.32 mmol) was added and the reaction mixture was stirred at 23° C. for 3 days. The reaction was quenched with NH4Cl (sat., 20 mL) and extracted with 9:1 CH2Cl2/iPrOH (50 mL; 25 mL×6). The combined organics were dried over MgSO4, and concentrated to an oil under reduced pressure from toluene. iPrOH (0.5 mL) was added, and the solution was seeded with crystals of the product. The resulting solids were washed with iPrOH (0.5 mL) and ether (2×2 mL). The mother liquor was then purified on silica (12 g) eluting with 0-3% MeOH/CH2Cl2. MS (ESI pos. ion) m/z (MH+): 217/219. Calc'd exact mass for C7H8BrNO2: 216. 1HNMR (400 MHz, CDCl3): δ 3.34 (br. s., 1H) 3.90-3.94 (m, 2H) 4.02-4.10 (m, 2H) 6.49 (d, J=9.59 Hz, 1H) 7.39 (dd, J=9.68, 2.64 Hz, 1H) 7.49-7.53 (m, 1H). 13C NMR (101 MHz, CDCl3) δ ppm 53.11, 61.04, 98.15, 121.80, 138.62, 143.04, 161.89

1. customThe reaction was quenched with NH4Cl (sat., 20 mL)
2. extractionextracted with 9:1 CH2Cl2/iPrOH (50 mL; 25 mL×6)
3. dry with materialThe combined organics were dried over MgSO4
4. concentrationconcentrated to an oil under reduced pressure from toluene
5. additioniPrOH (0.5 mL) was added
6. washThe resulting solids were washed with iPrOH (0.5 mL) and ether (2×2 mL)
7. customThe mother liquor was then purified on silica (12 g)
8. washeluting with 0-3% MeOH/CH2Cl2

ORD record

ord-e6be57b29c2445fb9b0baa2061bd9461

Source dataset

uspto-grants-2012_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08314087B2