Methanol → HCID 16658841, compound

Participants

Reaction Steps

A solution of 190 g (0.612 mole) of the crude (2R)-2-[2-fluoro-4-nitro(2,2,2-trifluoroethyl)anilino]-1-butanol in 1 Liter of dry THF was added dropwise to a stirred suspension of 36.77 g (0.919 mole, 1.5 eq) of sodium hydride in 1.5 L of dry THF under nitrogen atmosphere. After complete addition, the reaction mixture was refluxed for 3 h when TLC of the reaction mixture indicated complete conversion. After cooling to room temperature, 400 mL of methanol was added to destroy excess sodium hydride. The reaction mixture was poured into ice-cold water and extracted with ethyl acetate. The organic portions were combined, washed with brine and dried over MgSO4. After filtration, the solvents were evaporated under reduced pressure. The crude product thus obtained was purified by silica gel column chromatography (ethyl acetate:hexanes 1:9) to obtain (+)-(3R)-3-ethyl-3,4-dihydro-7-nitro-4-(2,2,2-trifluoroethyl)-2H-1,4-benzoxazine as a yellow crystalline solid. Yield 71 g (40%). [α]D=+56.6 (CHCl3, c 7.8); 1H NMR (CDCl3) δ 7.80 (1H, dd, J=2.56, 8.98), 7.71 (1H, d, J=2.57), 6.72 (1H, d, J=9.07), 4.34 (1H, dd, J=1.44, 11.02), 4.12 (1H, m), 4.06 (1H, dd, J=2.12, 11.04), 3.79 (1H, m), 3.37 (1H, m), 1.68 (2H, m), 1.00 (3H, t, J=7.54). 13C NMR: ppm 142.6, 139.1, 138.6, 126.1, 118.6, 112.6, 110.8, 64.9, 58.9, 50.6, 22.5 and 10.3.

Provenance & Evidence