Methyl iodide → 4-Chloro-3-fluoro-2-methylpyridine

Temperature

-78 °C

n-BuLi (8.5 ml of a 1.2 M soln in hexanes, 10.2 mmol) was added dropwise to a solution of 2,2,6,6-tetramethylpiperidine (1.73 ml, 10.2 mmol) in THF (30 ml) at 0° C. The mixture was then cooled to −78° C. and 4-chloro-3-fluoropyridine (1.0 ml, 10.2 mmol) was added dropwise over 15 minutes and then stirred for 25 minutes. MeI (0.64 ml, 10.2 mmol) was added dropwise at −78° C. and the resulting solution was left to warm to room temperature over several hours and quenched with saturated NaHCO3 (5 ml). The reaction was concentrated at reduced pressure, diluted with dichloromethane (50 ml), washed twice with saturated NaHCO3 (25 ml), dried (MgSO4), filtered and concentrated at reduced pressure. The residue was purified by FCC (pentane/diethyl ether with gradient, 9:1 to 8:2) to provide the title compound as colourless oil (833 mg, 56%).

1. waitthe resulting solution was left
2. temperatureto warm to room temperature over several hours
3. customquenched with saturated NaHCO3 (5 ml)
4. concentrationThe reaction was concentrated at reduced pressure
5. additiondiluted with dichloromethane (50 ml)
6. washwashed twice with saturated NaHCO3 (25 ml)
7. dry with materialdried (MgSO4)
8. filtrationfiltered
9. concentrationconcentrated at reduced pressure
10. customThe residue was purified by FCC (pentane/diethyl ether with gradient, 9:1 to 8:2)

ORD record

ord-f8e5221e55b7486283d1ea3bd4c917ba

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08691804B2