Phosphorus tribromide → 4-(Bromomethyl)-2-chloropyridine

Temperature

0 °C

(2-chloropyridin-4-yl)methanol (1.1 g, 7.3 mmol) is dissolved in 20 mL DCM; flushed with argon and cooled to 0° C. PBr3 (0.76 mL; 8.1 mmol) is added drop wise via a syringe (solution turned cloudy) and reaction mixture is stirred at RT for 3 h. Cooled to 0° C. and quenched with 5 mL water. The reaction mixture is adjusted to pH 7 by the addition of 2M K2CO3. The aqueous and organic layer are separated and the aqueous layer is extracted 3× with EtOAc. The organic layers are combined, dried over anhydrous sodium sulfate, filtered and deposited on silica. Column chromatography on silica gel (pre-washed with 1% NEt3), using a solvent gradient from hexanes to EtOAc lead to the isolation of the product as pale pink crystals (700 mg, 50% yield based on recovered starting material).

1. customflushed with argon
2. custom(solution turned cloudy) and reaction mixture
3. temperatureCooled to 0° C.
4. customquenched with 5 mL water
5. additionThe reaction mixture is adjusted to pH 7 by the addition of 2M K2CO3
6. customThe aqueous and organic layer are separated
7. extractionthe aqueous layer is extracted 3× with EtOAc
8. dry with materialdried over anhydrous sodium sulfate
9. filtrationfiltered

ORD record

ord-669142fb5c2842a098bf005bcdde39e6

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08816082B2