Methyl iodide → 2-Chloro-3-fluoro-6-(methoxymethyl)pyridine

To a suspension of sodium hydride (0.48 g, 12 mmol, 60% dispersion in mineral oil) in THF (15 mL) at 5° C. under nitrogen was added (6-chloro-5-fluoropyridin-2-yl)methanol (1.57 g, 9.28 mmol) suspended in THF (20 mL). The resulting suspension was stirred at this temperature for 30 minutes and then iodomethane (0.75 mL, 12 mmol) was added slowly. The reaction was warmed to room temperature over 48 hours. Further iodomethane was added (173 μL, 2.8 mmol) and stirring at room temperature was continued for 4 hours followed by the addition of further sodium hydride (110 mg, 2.75 mmol) at 5° C. The reaction was continued stirring for 24 hours before quenching with water (10 mL) and saturated aqueous ammonium chloride solution (20 mL) until pH=7. The solution was extracted with diethyl ether (3×50 mL). The organic layers were dried over sodium sulphate, and concentrated in vacuo. The residue was purified using silica gel column chromatography eluting with 20-50% DCM in pentane to afford the title compound (600 mg, 37% yield).

1. stirringstirring at room temperature
2. waitwas continued for 4 hours
3. stirringThe reaction was continued stirring for 24 hours
4. custombefore quenching with water (10 mL) and saturated aqueous ammonium chloride solution (20 mL) until pH=7
5. extractionThe solution was extracted with diethyl ether (3×50 mL)
6. dry with materialThe organic layers were dried over sodium sulphate
7. concentrationconcentrated in vacuo
8. customThe residue was purified
9. washeluting with 20-50% DCM in pentane

ORD record

ord-d3d2344b24254b24a5d967e4400cdb42

Source dataset

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09328096B2