3,4-Dihydro-2H-benzo[1,4]oxazine-6-carbonitrile

Synthesis

544-92-3

105655-01-4

928118-07-4

The general procedure for the synthesis of 3,4-dihydro-2H-benzo[b][1,4]oxazine-6-carbonitrile from cuprous cyanide and 6-bromo-3,4-dihydro-2H-benzo[1,4]oxazine was as follows: 6-bromo-3,4-dihydro-2H-benzo[1,4]oxazine (9D, 1.5 g, 7.05 mmol) and cuprous cyanide (CuCN, 1.58 g, 17.61 mmol) were placed in an anhydrous N,N-dimethylformamide (DMF, 15 mL) with stirring for 3 h at 130 °C and subsequently warmed up to 150 °C to continue the reaction overnight. 17.61 mmol) were placed in anhydrous N,N-dimethylformamide (DMF, 15 mL) and the reaction was stirred at 130 °C for 3 h. The temperature was then raised to 150 °C to continue the reaction overnight. Upon completion of the reaction, the mixture was cooled to room temperature and the reaction was quenched with water, followed by vacuum concentration. The concentrated residue was dissolved in a mixture of 2N sodium hydroxide (NaOH) solution and ethyl acetate (EtOAc, 100 mL) and stirred in a sonicator for 1 hour. The precipitate was collected by filtration and washed with ethyl acetate. The filtrate and washings were combined and extracted with ethyl acetate (2 x 80 mL). The organic layers were combined, dried with anhydrous magnesium sulfate (MgSO4), filtered and concentrated in vacuum to afford the target product 3,4-dihydro-2H-benzo[b][1,4]oxazine-6-carbonitrile (12A, 1.062 g, 94% yield).

References