Dichloromethane → 4-Ethyl-2-(4-nitrophenyl)morpholine

Participants

Reaction Steps

Combined 2-Bromo-1-(4-nitro-phenyl)-ethanone (5.0 g, 0.020 mol) with Methylene chloride (100 mL, 2 mol) and treated with 2-Ethylamino-ethanol (2.0 mL, 0.020 mol) and N,N-Diisopropylethylamine (3.6 mL, 0.021 mol), stirred at rt, 3 h. Treated the mixture with Triethylsilane (10.33 mL, 0.06468 mol) and then Trifluoroacetic Acid (52.5 mL, 0.681 mol) and heated to 40° C. and stirred under nitrogen overnight. Concentrated and partitioned between ice/water and heptane, stirred vigorously for 10 min. Decanted off the heptane to remove silyl byproducts, repeated. Basified with solid K2CO3. Extracted with EtOAc, the organics were washed with brine, dried (MgSO4), filtered and concentrated onto Celite and purified by ISCO chromatography (80 g, SiO2, gradient elution: 100% Hex to 100% EtOAc to 10% MeOH/EtOac), (+/−)-4-Ethyl-2-(4-nitro-phenyl)-morpholine was isolated as red waxy solid (2.45 grams). 1H-NMR (CDCl3) δ 8.22 (d, J=8.8 Hz, 2H), 7.76 (d, J=8.8 Hz, 2H), 4.69 (dd, J=10.5, 2.3 Hz, 1H), 4.10 (dd, J=11.5, 2.0, 1H), 3.90-3.84 (m, 1H), 4.11-4.08 (m, 1H), 3.00 (d, J=11.5 Hz, 1H), 2.87 (d, J=9.9 Hz, 1H), 2.48 (dd, J=7.2, 14.4 Hz, 2H), 2.27-2.20 (m, 1H), 1.99 (t, J=10.7 Hz, 1H), 1.13 (t, J=7.2 Hz, 3H); LC/MS (ESI+): 237 (M+H).

Provenance & Evidence