Hydrochloric Acid → 6,7-Difluoro-2-methylquinoline

Participants

Reaction Conditions

Reaction Steps

Crotonaldehyde (226.34 g, 3.23 mol) in 100 mL of 2-butanol was added dropwise to a refluxing solution of 3,4-difluoroaniline (417.27 g, 3.23 mol), p-chloranil (794.65 g, 3.23 mol) and HCl conc. (808 mL) in 5.4 L of 2-butanol. After 2 hours of heating 2.7 L of solvent was removed under vacuum at ca. 60° C. Then 2 L of toluene was added to the reaction mixture followed by removal of 2.5-3 L of solvent or until a very pasty solid formed. THF (2 L) was added and the mixture heated 30 min. after which it was cooled to 0° C. The solid was collected and washed with THF until pure by tlc. The solid was then dissolved in aq. K2CO3 /EtOAc and the organic phase separated. The aqueous phase was extracted with EtOAc (2×) and the organic phases combined, dried over MgSO4 and the solvent removed. The product was crystallized in the minimum amount of EtOAc to give 328.08 g (57%) of the title compound.

Provenance & Evidence