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

Yield:928118-07-4 94%

Reaction Conditions:

Stage #1: copper(I) cyanide;6-bromo-3, 4-dihydro-2H-benzo[β][1, 4]oxazine in N,N-dimethyl-formamide at 130 - 150;
Stage #2: with sodium hydroxide in water;ethyl acetate; for 1 h;Sonographic reaction;

Steps:

12.1

A mixture of 6-bromo-3,4-dihydro-2H-benzo[1,4]oxazine (9D, 1.5 g, 7.05 mmol) and CuCN (1.58 g, 17.61 mmol) in anhydrous DMF (15 mL) was stirred at 130° C. for 3 h and then at 150° C. overnight. Then the mixture was cooled to RT, quenched with water and concentrated under vacuum. The residue was taken up in 2N NaOH and EtOAc (100 mL) and then agitated in a sonicator for 1 h. The precipitate was filtered off and washed with EtOAc. The filtrate and washings were combined and extracted with EtOAc (2×80 mL). The organic layer was dried (MgSO₄), filtered and concentrated under vacuum to give compound 12A (1.062 g, 94%).

References:

US2007/93477,2007,A1 Location in patent:Page/Page column 27-28