Thionyl Chloride → (5-Bromo-3-pyridinyl)methanol

Temperature

0 °C

Under a nitrogen atmosphere, a solution of 5-bromonicotinic acid (5.05 g, 25.0 mmol) and thionyl chloride (10 mL) was stirred and heated. The excess thionyl chloride was removed by distillation, and the residue was dried briefly under high vacuum. To the resulting light-yellow solid in dry tetrahydrofuran (40 mL) was added sodium borohydride (1.90 g, 50.0 mmol) at 0° C. under a nitrogen atmosphere. The mixture was stirred 1 h at 0° C. and allowed to warm to ambient temperature. The mixture was added to a cold, saturated aqueous NH4Cl solution (100 mL) and extracted with diethyl ether (3×50 mL). The combined ether extracts were dried (Na2SO4), filtered, and concentrated by rotary evaporation to a semisolid (2.77 g). Thin layer chromatography analysis on silica gel indicated mostly 5-bromonicotinic acid; therefore the semisolid was partitioned between ether and saturated aqueous NaHCO3 solution. The ether layer was separated and concentrated by rotary evaporation to a residue (0.75 g). Purification by column chromatography on silica gel, eluting with ethyl acetate-hexane (1:1, v/v) afforded 379 mg (8.1%) of 3-bromo-5-hydroxymethylpyridine.

1. temperatureheated
2. customThe excess thionyl chloride was removed by distillation
3. customthe residue was dried briefly under high vacuum
4. temperatureto warm to ambient temperature
5. extractionextracted with diethyl ether (3×50 mL)
6. dry with materialThe combined ether extracts were dried (Na2SO4)
7. filtrationfiltered
8. concentrationconcentrated by rotary evaporation to a semisolid (2.77 g)
9. customtherefore the semisolid was partitioned between ether and saturated aqueous NaHCO3 solution
10. customThe ether layer was separated
11. concentrationconcentrated by rotary evaporation to a residue (0.75 g)
12. customPurification by column chromatography on silica gel
13. washeluting with ethyl acetate-hexane (1:1

ORD record

ord-670ff1254b3f4e6690c883ca8c84e0ef

Source dataset

uspto-grants-2003_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06531606B1