Hydrochloric Acid → 2,6-Dichloro-5-fluoro-4-methylpyridine-3-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

To a solution of 0.516 moles of lithiodiisopropyl amine in 390 mL hexane and 200 mL tetrahydrofuran, cooled to -70° C., was added dropwise a solution of 40 g (0.229 moles) 2,6-dichloro-5-fluoronicotinic acid in 600 mL tetrahydrofuran, over a 1-hour period. The reaction mixture was stirred at -70° C. for 1 hour, then warmed to -60° C. for 1.5 hours at which time a light colored precipitate formed. The slurry was briefly warmed to -50° C., then recooled to -70° C., at which point a solution of 84 mL (1.34 moles) methyl iodide in 90 mL tetrahydrofuran was added dropwise. After the addition was complete, the reaction mixture was allowed to slowly warm to -20° C. over approximately 1 hour. The solution was acidified with dilute HCl pH 1-2 diluted with diethyl ether and allowed to warm to room temperature. The aqueous layer was extracted twice with ether. The combined ether washes were washed with H2O, dried with MgSO4, and evaporated in vacuo to yield a crude solid. The crude material was recrystallized from toluene to yield 31.7 g of the title compound.

Provenance & Evidence