Hydrochloric Acid → 4-[(9aS)-hexahydropyrazino[2,1-c][1,4]oxazin-8(1H)-yl]-2-(methyloxy)aniline

Participants

Reaction Steps

To (9aS)-8-[3-(methyloxy)-4-nitrophenyl]octahydropyrazino[2,1-c][1,4]oxazine (0.196 g, 0.660 mmol) in dioxane (8 mL) and THF (4 mL) cooled to 0° C. was added tin(II) chloride (0.544 g, 2.86 mmol) in HCl (2.20 mL, 37% in water, 24.6 mmol) dropwise. The reaction warmed to rt and stirred overnight. An additional amount of tin(II) chloride (1.00 g, 5.27 mmol) in HCl (4.40 mL, 37% in H2O, 49.1 mmol) was added to the reaction. When complete by TLC, the reaction was cooled to 0° C. and quenched with 6N NaOH (50 mL). The mixture was poured into H2O/EtOAc and separated. The organic layer was washed with brine and the resultant aqueous layer was back extracted with EtOAc. The combined organic layer was dried (MgSO4) and concentrated to provide the title compound of step B (0.170 g, 0.640 mmol, 98%). 1H NMR (400 MHz, DMSO-d6) b ppm 1.47 (dt, J=14.9, 6.5 Hz, 1H), 1.65-1.74 (m, 1H), 2.14-2.25 (m, 1H), 2.26-2.31 (m, 1H), 2.55-2.66 (m, 1H), 2.74 (d, J=10.8 Hz, 1H), 3.10 (t, J=10.4 Hz, 1H), 3.17 (d, J=11.5 Hz, 1H), 3.31 (d, J=11.7 Hz, 1H), 3.37 (q, J=6.2 Hz, 1H), 3.47 (td, J=11.3, 2.1 Hz, 1H), 3.60 (t, J=6.7 Hz, 1H), 3.63-3.74 (m, 4H), 4.41 (t, J=5.3 Hz, 1H), 4.46 (s, 1H), 6.23 (dd, J=8.3, 2.5 Hz, 1H), 6.42-6.50 (m, 2H).

Provenance & Evidence