Methanesulfonyl chloride → 6-Chloro-2-fluoro-3-methanesulfonyl-pyridine

Temperature

0 °C

2-Chloro-6-fluoropyridine (500 mg, 3.8 mmol) was taken up in tetrahydrofuran (19 mL) and cooled to −78° C. n-Butyllithium (2.4 mL, 3.8 mmol) was added dropwise over 10 minutes. The solution was stirred for 30 minutes and methanesulfonyl chloride (0.3 mL, 3.8 mmol) was added dropwise over 15 minutes. The resulting mixture was stirred at −78° C. for 2 hours and then warmed to 0° C. and stirred for 2 hours followed by an additional 2 hours at room temperature. The reaction was quenched with saturated aqueous ammonium chloride and extracted with ethyl acetate (2×). The combined organics were dried over magnesium sulfate, filtered, and concentrated in vacuo. The crude residue was purified by flash chromatography (silica, 0-75% ethyl acetate/hexanes) to afford the title compound as a light yellow oil.

1. additionwas added dropwise over 10 minutes
2. stirringThe resulting mixture was stirred at −78° C. for 2 hours
3. stirringstirred for 2 hours
4. waitfollowed by an additional 2 hours at room temperature
5. customThe reaction was quenched with saturated aqueous ammonium chloride
6. extractionextracted with ethyl acetate (2×)
7. dry with materialThe combined organics were dried over magnesium sulfate
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customThe crude residue was purified by flash chromatography (silica, 0-75% ethyl acetate/hexanes)

ORD record

ord-b15d5df19849419b8ea226937a9171ae

Source dataset

uspto-grants-2013_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08367706B2