Phosphorus oxychloride → Methyl 5-bromo-6-chloropicolinate

Temperature

60 °C

A mixture of 5-bromo-pyridine-2-carboxylic acid methyl ester (CAN 29682-15-3, 50 g, 0.23 mol) and m-CPBA (CAN 937-14-4, 80 g, 0.46 mol) in 400 mL dry methylene chloride was heated to 60° C. for 20 h. After that, the mixture was quenched with saturated sodium sulfite solution and extracted with ethyl acetate (2×200 mL). The organic layer was washed with brine (2×200 mL) and evaporated to dryness. The residue was purified by column chromatography (silica gel, 300 g, eluting with 15% ethyl acetate in petroleum ether) to obtain a brown oil. The brown oil, 5-bromo-2-(methoxycarbonyl)pyridine 1-oxide (30 g, 0.13 mol) was added into phosphoryl trichloride (CAN 10025-87-3, 80 mL) at 0° C. over 1 h, then the mixture was heated to 95° C. for 1 h. After that the mixture was evaporated to dryness, the residue was dissolved in water (50 mL), extracted with ethyl acetate (3×50 mL) and the organic layer was evaporated to dryness to obtain the product as a white solid (19 g, 59%); MS (EI): m/e=249.9 [M+H]+.

1. customAfter that, the mixture was quenched with saturated sodium sulfite solution
2. extractionextracted with ethyl acetate (2×200 mL)
3. washThe organic layer was washed with brine (2×200 mL)
4. customevaporated to dryness
5. customThe residue was purified by column chromatography (silica gel, 300 g, eluting with 15% ethyl acetate in petroleum ether)
6. customto obtain a brown oil
7. temperaturethe mixture was heated to 95° C. for 1 h
8. customAfter that the mixture was evaporated to dryness
9. dissolutionthe residue was dissolved in water (50 mL)
10. extractionextracted with ethyl acetate (3×50 mL)
11. customthe organic layer was evaporated to dryness

ORD record

ord-913a99fef4ba4cdeb75c356dd6c5f191

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09321727B2