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

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Reaction Steps

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).

Provenance & Evidence