Tetrahydrofuran → 2H-3,1-Benzoxazin-2-one, 1,4-dihydro-4,4-dimethyl-8-methoxy-

Temperature

50 °C

To a solution of 2-amino-3-methoxybenzoic acid (5 g, 30 mmol) in anhydrous THF (100 mL) was added at ambient temperature under a blanket of nitrogen methylmagnesium bromide (3.0 M in THF, 50 mL, 150 mmol). The reaction mixture was heated at 50° C. for 18 hours, cooled to rt, and treated with a saturated aqueous ammonium chloride solution (50 mL). Ethyl acetate (100 mL) was added and organic layer was separated, dried (MgSO4), and evaporated. The residue was dissolved in anhydrous THF (100 mL) and treated at ambient temperature under nitrogen with 1,1′-carbonyldiimidazole (5.4 g, 33 mmol). After 24 hours, the mixture was quenched with 1N aqueous hydrogen chloride solution (30 mL). Ethyl acetate (100 mL) was added, organic layer was separated, dried (MgSO4), and evaporated. The residue was purified by a silica gel column chromatography (hexane:ethyl acetate/3:1) to afford 8-methoxy-4,4-dimethyl-1,4-dihydro-2H-3,1-benzoxazin-2-one as white solid (3.5 g, 56%): MS (ESI) m/z 208 [M+H]+.

1. temperaturecooled to rt
2. customorganic layer was separated
3. dry with materialdried (MgSO4)
4. customevaporated
5. dissolutionThe residue was dissolved in anhydrous THF (100 mL)
6. customthe mixture was quenched with 1N aqueous hydrogen chloride solution (30 mL)
7. additionEthyl acetate (100 mL) was added
8. customorganic layer was separated
9. dry with materialdried (MgSO4)
10. customevaporated
11. customThe residue was purified by a silica gel column chromatography (hexane:ethyl acetate/3:1)

ORD record

ord-571bac03bced488689e7e621305a237d

Source dataset

uspto-grants-2002_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06444668B1