Chloroacetyl chloride → 7-hydroxy-3,4-dihydro-2H-1,4-benzoxazin-3-one

To a solution of 4-aminobenzene-1,3-diol (2.5 g, 20 mmol) in tetrahydrofuran (30 mL), sodium bicarbonate (2.52 g, 30 mmol) was added and stirred for 10 minutes. Then 2-chloroacetyl chloride (1.6 mL, 20 mmol) was added to the above mixture. The resulting reaction mixture was stirred at ambient temperature for 18 hours. A precipitate formed and removed by filtration. The filtrate was concentrated to give the oil residue. The resulting residue was treated with 10% NaOH aqueous solution for 30 minutes. The aqueous layer was acidified with 1N hydrogen chloric acid and extracted with ethyl acetate, washed with brine and water. The organic layer was separated, dried (Na2SO4) and concentrated. The crude material was purified by silica gel chromatography using a 90:10 mixture of hexane and ethyl acetate as eluent to afford the title product as a white solid (1.4 g, 42% yield). 1H NMR (400 MHz, d6-DMSO) δ: 10.42 (1H, s), 9.23 (1H, s), 6.69 (1H, m), 6.35 (2H, m), 4.47 (2H, s). MS m/z: 164.01 [M+H]+.

1. customThe resulting reaction mixture
2. stirringwas stirred at ambient temperature for 18 hours
3. customA precipitate formed
4. customremoved by filtration
5. concentrationThe filtrate was concentrated
6. customto give the oil residue
7. extractionextracted with ethyl acetate
8. washwashed with brine and water
9. customThe organic layer was separated
10. dry with materialdried (Na2SO4)
11. concentrationconcentrated
12. customThe crude material was purified by silica gel chromatography
13. additiona 90:10 mixture of hexane and ethyl acetate as eluent

ORD-Eintrag

ord-2414a88c50df4c5788e0cd13bdb51ac1

Quelldatensatz

uspto-grants-2014_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08680139B2