Phosphorus tribromide → 6-Bromopyridine-3-carbonitrile

Temperature

145 °C

6-Chloronicotinonitrile (13.8 g, 100 mmol) was heated at 145° C. in phosphorus tribromide (150 mL) for 32 h. After cooling, the mixture was concentrated in vacuo. To the residue was added phosphorus tribromide (150 mL), and the mixture was heated at 145° C. for another 32 h. After cooling, the mixture was concentrated in vacuo, and an ice-water mixture (500 mL) was added. Sodium bicarbonate was added to neutralize the mixture, and the product was extracted with ethyl acetate (3×250 mL). The combined organic extracts were washed with brine and dried over magnesium sulfate. The solvent was removed in vacuo, and the residue was chromatographed (hexanes-ethyl acetate) to give 14.9 g (81%) of 6-bromonicotinonitrile as a white solid: 1H NMR (400 MHz, CDCl3) δ7.66 (d, J=11.0 Hz, 1H), 7.80 (dd, J=3.1, 11.0 Hz, 1H), 8.67 (d, J=3.1 Hz, 1H); MS (M+H)+ m/z=183.0, 185.0.

1. temperatureAfter cooling
2. concentrationthe mixture was concentrated in vacuo
3. additionTo the residue was added phosphorus tribromide (150 mL)
4. temperatureAfter cooling
5. concentrationthe mixture was concentrated in vacuo
6. additionan ice-water mixture (500 mL) was added
7. additionSodium bicarbonate was added
8. extractionthe product was extracted with ethyl acetate (3×250 mL)
9. washThe combined organic extracts were washed with brine
10. dry with materialdried over magnesium sulfate
11. customThe solvent was removed in vacuo
12. customthe residue was chromatographed (hexanes-ethyl acetate)

ORD record

ord-016ad3dc5d364bb2aedd6b9d3b883b20

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08697870B2