Toluene → HCID 59568636, compound

Participants

Reaction Steps

To a mixture of 2,6-difluoronicotinic acid (20.0 g), DMF (4 mL) and toluene (400 mL) was added oxalyl dichloride (11.9 mL) at 0° C. The mixture was stirred at room temperature for 1 hr, and the solvent was evaporated under reduced pressure. THF (120 mL) was added to the residue, and a solution of N-benzylethanolamine (20.9 g) in THF was added. 8M Aqueous sodium hydroxide solution (40 mL) was added at 0° C., and the resulting mixture was stirred at room temperature for 16 hr. Ethyl acetate and water were added, and the organic layer was washed with water and saturated brine and dried, and the solvent was evaporated under reduced pressure. THF (100 mL) was added to the obtained residue (34.5 g), and a suspension of sodium hydride (5.70 g) in THF (400 mL) was added dropwise at 0° C. The mixture was stirred at room temperature for 16 hr, and water was added. The resulting product was extracted with ethyl acetate, the organic layer was washed with water and saturated brine and dried, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (solvent gradient; 50→100% ethyl acetate/hexane) to give 4-benzyl-8-fluoro-3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one (11.2 g, 33%) as a yellow oil.

Provenance & Evidence