Dichloromethane → 4-Bromo-2-methyl-3-nitropyridine

A mixture of 2-methyl-3-nitropyridin-4-ol (2 g, 12.98 mmol) and phosphorus oxybromide (24.93 g, 87 mmol) was melted at 140° C. in a pressure vessel over 3 hours. The reaction mixture was cooled, poured into chloroform (100 mL) and ice water (100 mL). The layers were separated and the organic layer was washed with water (2×25 mL), saturated sodium bicarbonate (2×75 mL), dried over magnesium sulfate, filtered, and concentrated to give an oil. The oil was treated with a mixture of dichloromethane and chloroform (50 mL, 3:1) to give a solid which was filtered and dried under vacuum. The filtrate was reduced in volume by 50% under vacuum, loaded on a silica column and eluted with 2% methanol in dichloromethane to give additional product which was concentrated and combined with the initial batch to give 4-bromo-2-methyl-3-nitropyridine (1.4 g, 6.45 mmol, 49.7% yield); MS [M+H] found 217.0. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.53 (s, 3H) 7.88 (dd, J=5.31, 0.51 Hz, 1H) 8.52-8.59 (m, 1H).

1. customover 3 hours
2. temperatureThe reaction mixture was cooled
3. customThe layers were separated
4. washthe organic layer was washed with water (2×25 mL), saturated sodium bicarbonate (2×75 mL)
5. dry with materialdried over magnesium sulfate
6. filtrationfiltered
7. concentrationconcentrated
8. customto give an oil
9. customto give a solid which
10. filtrationwas filtered
11. customdried under vacuum
12. washeluted with 2% methanol in dichloromethane
13. customto give additional product which
14. concentrationwas concentrated

ORD record

ord-5031d8a670814e22bfef402a880fc37c

Source dataset

uspto-grants-2015_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09073918B2