Methyl iodide → 2-Chloro-3-methoxypyridine

To a stirred solution of 2-chloro-3-hydroxypyridine (25.4 g, 196 mmol) in dry DMF (250 mL), at 0° C., was added sodium methoxide (11.5 g, 213 mmol). After 5 min, the reaction mixture was allowed to warm to RT. After 1 hour, the mixture was cooled to 0° C. and iodomethane (24 mL, 386 mmol) was added. The reaction mixture was stirred at 0° C. for 5 minutes, before allowing to warm to RT. After 2 hours, the reaction mixture was concentrated under reduced pressure. The resultant residue was partitioned between diethyl ether and water. The aqueous phase was isolated and extracted twice with diethyl ether. The combined organic extracts were washed with water, brine, dried (Na2SO4), filtered and concentrated in vacuo to give the title compound (22.2 g, 79%) as an orange solid. LCMS (Method A): RT=2.76 min, [M+H]+=144/146.

1. waitAfter 1 hour
2. temperaturethe mixture was cooled to 0° C.
3. temperatureto warm to RT
4. waitAfter 2 hours
5. concentrationthe reaction mixture was concentrated under reduced pressure
6. customThe resultant residue was partitioned between diethyl ether and water
7. customThe aqueous phase was isolated
8. extractionextracted twice with diethyl ether
9. washThe combined organic extracts were washed with water, brine
10. dry with materialdried (Na2SO4)
11. filtrationfiltered
12. concentrationconcentrated in vacuo

ORD record

ord-c08ab2ebc3404938a14ddafb0f6dc8c4

Source dataset

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08546376B2