3,5-Dimethoxybenzoyl chloride → (3,5-dimethoxy-phenyl)-(4-methyl-3,4-dihydro-2H-benzo[1,4]oxazin-7-yl)-methanone

To a solution of 7-bromo-4-methyl-3,4-dihydro-2H-benzo[1,4]oxazine (0.9 g, 3.9 mmol) in THF (10 mL) was added n-butyllithium (1.3 mL, 2.5 N, 3.3 mmol) at −78° C. After 10 min, the solution was added to a solution of 3,5-dimethoxy-benzoyl chloride (650 mg, 3.2 mmol) in THF (10 mL) at −78° C. After 1 h, the cold bath was removed and the mixture was allowed to warm to room temperature. To the mixture was added iso-propanol (2 mL), water (30 mL) and ethyl acetate (50 mL). The aqueous layer was extracted with ethyl acetate (50 mL). The combined organic layers was washed with sodium hydrogen carbonate (50 mL, sat), brine (50 mL) and dried over magnesium sulfate. Removal of solvent and chromatography (Silica Gel) gave (3,5-dimethoxy-phenyl)-(4-methyl-3,4-dihydro-2H-benzo[1,4]oxazin-7-yl)-methanone as a yellow solid (320 mg, 30% yield): 1H NMR (CDCl3) δ 2.86 (s, 3H, CH3), 3.42 (t, J=5 Hz, 2H, CH2), 3.82 (s, 6H, 2CH3), 4.27 (t, J=4 Hz, 2H, CH2), 6.60-6.64 (m, 2H, Ar), 6.85 (d, J=2 Hz, 2H, Ar), 7.36 (d, J=8 Hz, 1H, Ar), 7.43 (dd, J=2, 9 Hz, 1H, Ar).

1. waitAfter 1 h
2. customthe cold bath was removed
3. additionTo the mixture was added iso-propanol (2 mL), water (30 mL) and ethyl acetate (50 mL)
4. extractionThe aqueous layer was extracted with ethyl acetate (50 mL)
5. washThe combined organic layers was washed with sodium hydrogen carbonate (50 mL, sat), brine (50 mL)
6. dry with materialdried over magnesium sulfate
7. customRemoval of solvent and chromatography (Silica Gel)

ORD record

ord-a13f8cfd959c4c3b8f5b56578bb8e79b

Source dataset

uspto-grants-2008_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07468446B2