Sodium Hydroxide → 3-Methyl-3,4-dihydro-2H-1,4-benzoxazine

Temperature

50 °C

To a solution of 2H-1,4-benzoxazin-3(4H)-one (2.00 g, 13.4 mmol) in tetrahydrofuran (20 ml) was added dropwise at 5° C. a THF solution of methylmagnesium chloride (17.9 ml, 3 M, 53.7 mmol) and the reaction mixture was then stirred at 50° C. for 90 min. The reaction mixture was then cooled to 5° C. and quenched by dropwise addition of 20 ml acetic acid. Sodium borohydride (1.27 g, 33.5 mmol) was then added portionwise and the mixture was stirred at room temperature overnight. The resulting suspension was then cooled to 0° C. and 3 N aq. sodium hydroxide solution was added dropwise until the mixture was pH 10. Ethyl acetate was then added, the phases separated, and the organic phase dried over sodium sulphate and concentrated in vacuo. The residue was purified by chromatography on silica gel (eluant: heptane/ethyl acetate gradient) to yield the title compound as a colorless oil (0.92 g, 46%); MS (ISP): 150.3 ([M+H]+).

1. temperatureThe reaction mixture was then cooled to 5° C.
2. customquenched by dropwise addition of 20 ml acetic acid
3. stirringthe mixture was stirred at room temperature overnight
4. temperatureThe resulting suspension was then cooled to 0° C.
5. customthe phases separated
6. dry with materialthe organic phase dried over sodium sulphate
7. concentrationconcentrated in vacuo
8. customThe residue was purified by chromatography on silica gel (eluant: heptane/ethyl acetate gradient)

ORD record

ord-4f5fa2ca77274077b24abc3683f37896

Source dataset

uspto-grants-2010_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07834044B2