Methane → tert-Butyl 2-(4-aminophenyl)morpholine-4-carboxylate

Participants

Reaction Steps

tert-Butyl 2-(4-nitrophenyl)morpholine-4-carboxylate (I87) (100 mg, 0.324 mmol), activated charcoal (20 mg), iron(III) chloride hexahydrate (9 mg, 10 mol %), methanol (1 mL) and hydrazine hydrate (I62 mg, 1.62 mmol @ 50%) were refluxed together for five hours. The mixture was filtered through cotton, and the cotton washed with DCM (5 mL). The filtrate was evaporated, and redissolved in 95% ethanol (3 mL) and ethyl acetate (2 mL). A solution of ammonium chloride (173 mg. 3.24 mmol) in water (1 mL) was added, followed by indium powder (153 mg, 1.30 mmol). The mixture was refluxed for four hours then filtered. The collected solids were washed with DCM (20 mL) and the combined filtrates then diluted with water (10 mL) and saturated sodium bicarbonate (10 mL). The aqueous phase was washed with DCM (2×25 mL), the combined DCM extracts dried (phase separation filter) and evaporated. The residue was dissolved in 95% ethanol (3 mL), and treated at reflux with further indium powder (153 mg, 1.30 mmol) and ammonium chloride (173 mg. 3.24 mmol) in water (1 mL). After three hours the mixture was diluted with water (10 mL) and filtered. The collected solids were washed sequentially with ethyl acetate (25 mL) and saturated sodium bicarbonate (10 mL). The filtrate aqueous phase was separated, and washed with ethyl acetate (2×25 mL). The combined organic extracts were washed with brine (50 mL), dried and evaporated. The residue was chromatographed (12 g silica cartridge, 0-100% ethyl acetate/petroleum benzine 40-60° C.) to give the title compound (I88) (51.4 mg, 57% yield) as a yellow oil; 1H NMR (400 MHz, CDCl3) δ 7.19-7.12 (m, 2H), 6.71-6.63 (m, 2H), 4.33-4.25 (m, 1H), 4.03-3.85 (m, 3H), 3.73-3.60 (m, 3H), 3.02 (s, 1H), 2.84 (s, 1H). LCMS Method C: rt: 4.72 min; m/z 179.1 [M-Boc+2H]+.

Provenance & Evidence