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

Temperatur

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-Eintrag

ord-a2c83055951e47558c283289bd321e91

Quelldatensatz

uspto-grants-2004_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06713478B2