Acetic Acid → 6-Cyclopropylamino-4-(3-methoxy-propyl)-2,2-dimethyl-4H-benzo[1,4]oxazin-3-one

Participants

Reaction Conditions

Reaction Steps

At room temperature, a methanolic solution (33 ml) of 6-amino-4-(3-methoxy-propyl)-2,2-dimethyl-4H-benzo[1,4]oxazin-3-one (4.13 g, 15.6 mmol) is treated with AcOH (8.3 ml) and [(1-ethoxycycopropyl)-oxy]trimethylsilane (3.1 ml, 15.6 mmol), warmed to 70° C., stirred for 1.5 h under reflux. At the same temperature, to this mixture is added dropwise a methanolic solution (5.5 ml) of NaBH3CN (1.10 g, 17.5 mmol) over 5 min, and the resulting mixture is stirred at 70° C. under reflux for 2 h, and treated with CH2Cl2 (100 ml) and 5N NaOH (50 ml). After the separation of the both layers, the aq. layer is extracted with CH2Cl2 (3×30 ml). The combined org. layer is washed with brine (50 ml), dried (Na2SO4), and evaporated. A SiO2 flash chromatography (200 g, hexane/EtOAc 3:2) gives the title compound (3.03 g, 64%) as light yellow solid. Rf(hexane/EtOAc 3:2) 0.48. 1H-NMR (400 MHz, CDCl3) 0.47-0.54 (m, 2 H), 0.68-0.73 (m, 2 H), 1.55 (s), 1.88-1.96 (m, 2 H), 2.36-2.43 (m, 1 H), 3.34 (s), 3.44 (t, J=6.0), 3.97 (t, J=9.0), 4.09 (br. s), 6.45 (dd, J=9.0, 0.4), 6.53 (d, J=0.4), 6.80 (d, J=9.0). 13C-NMR (100 MHz, CDCl3) 169.2 (s), 144.3 (s), 135.5 (s), 129.6 (s), 118.1 (d), 107.9 (d), 99.9 (d), 77.2 (s), 70.1 (t), 58.7 (q), 39.2 (t), 27.6 (t), 25.7 (d), 23.6 (2q), 7.3 (2t).

Provenance & Evidence