Methyl 5-bromopyridine-3-carboxylate → (5-Bromo-3-pyridinyl)methanol

Temperature

0 °C

A suspension of 5-bromo-nicotinic acid methyl ester (example 26d) (10 g, 46.29 mmol) in anhydrous EtOH (100 ml) was cooled to 0° C. and NaBH4 (4.03 g, 106.47 mmol) was added in portions within 15 min. After stirred at 0° C. for 1 hour the ice bath was removed and stirring was continued at room temperature for 3 hours, then the reaction mixture was heated to reflux overnight. The solvent was evaporated and acetone (50 mL) was added and the solution stirred for 30 minutes then the acetone was evaporated. Saturated aqueous K2CO3 (50 mL) was added and the mixture was refluxed for 1 hour then diluted with water (100 mL) and extracted with DCM. The organic phase was dried over MgSO4, filtered and evaporated. The residue was chromatographed on silica gel (5% MeOH in DCM) to give 4.78 g of pure (5-bromopyridin-3-yl)methanol as a light yellow oil. Yield 55%. 1H NMR (400 MHz, CDCl3): 2.60 (t, 1H); 4.73-4.74 (d, 2H), 7.90 (s, 1H,), 8.47 (s, 1H), 8.57 (s, 1H).

1. customwas removed
2. temperaturethe reaction mixture was heated
3. temperatureto reflux overnight
4. customThe solvent was evaporated
5. additionacetone (50 mL) was added
6. stirringthe solution stirred for 30 minutes
7. customthe acetone was evaporated
8. additionSaturated aqueous K2CO3 (50 mL) was added
9. temperaturethe mixture was refluxed for 1 hour
10. additionthen diluted with water (100 mL)
11. extractionextracted with DCM
12. dry with materialThe organic phase was dried over MgSO4
13. filtrationfiltered
14. customevaporated
15. customThe residue was chromatographed on silica gel (5% MeOH in DCM)

ORD record

ord-d25f29d64f68489bb1d50eb77592b37a

Source dataset

uspto-grants-2010_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07842324B2