Sodium hydride → 3,4-Dihydro4-(2-dimethylaminoethyl)-6-nitro-2H-1,4-benzoxazine

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Reaction Steps

A solution of 6-nitro-3,4-dihydro-2H-benzo[b][1,4]oxazine (1.0 g, 5.55 mmol) in anhydrous DMF (25 mL) under argon was cooled and treated portionwise with sodium hydride (0.677 g, 16.93 mmol) at 5-10° C. 2-chloro-N,N-dimethylethanamine hydrochloride (1.599 g, 11.10 mmol) was added portionwise at 5-10° C., and the resulting heterogeneous red-brown mixture was allowed to warm to room temperature. After 3 hours at room temperature, the mixture was heated to 90° C. and stirred for 30 minutes. The mixture was cooled to room temperature, quenched by the addition of water (25 mL), and diluted with EtOAc. A small amount of 1 N NaOH was added to basify the mixture to pH ˜9-10. The organic layer was separated, and the aqueous layer was further extracted with EtOAc. The combined organic layers were washed with brine (×2), dried (Na2SO4), filtered, and concentrated to afford a dark red oil. The material was purified on silica gel, eluting with 5% MeOH/CH2Cl2, to yield the title compound as a dark orange-red oil (458 mg, 32.8%). 1H NMR (DMSO-d6) δ 7.49-7.39 (m, 2H), 6.87-6.84 (m, 1H), 4.27-4.25 (m, 2H), 3.50-3.37 (m, 4H), 2.43 (t, 2H, J=6.7 Hz), 2.19 (s, 6H); ESI-MS (m/z, %): 252 (MH+, 100).

Provenance & Evidence