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

Participants

Reaction Conditions

Reaction Steps

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%).

Provenance & Evidence