Toluene → HCID 59568636, compound

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.

1. customthe solvent was evaporated under reduced pressure
2. additionTHF (120 mL) was added to the residue
3. additiona solution of N-benzylethanolamine (20.9 g) in THF was added
4. addition8M Aqueous sodium hydroxide solution (40 mL) was added at 0° C.
5. stirringthe resulting mixture was stirred at room temperature for 16 hr
6. additionEthyl acetate and water were added
7. washthe organic layer was washed with water and saturated brine
8. customdried
9. customthe solvent was evaporated under reduced pressure
10. additionTHF (100 mL) was added to the obtained residue (34.5 g)
11. additiona suspension of sodium hydride (5.70 g) in THF (400 mL)
12. additionwas added dropwise at 0° C
13. stirringThe mixture was stirred at room temperature for 16 hr
14. additionwater was added
15. extractionThe resulting product was extracted with ethyl acetate
16. washthe organic layer was washed with water and saturated brine
17. customdried
18. customthe solvent was evaporated under reduced pressure
19. customThe residue was purified by silica gel column chromatography (solvent gradient; 50→100% ethyl acetate/hexane)

ORD record

ord-a1480aa88ef646a0a31ed7c13c328bb4

Source dataset

uspto-grants-2012_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08329687B2