Ammonia → HCID 18787107, compound

Participants

Reaction Conditions

Reaction Steps

Sodium hydride (60% dispersion in mineral oil, 0.90 g, 25.2 mmol) was added to a stirred, cooled (0° C.) solution of N-(3-bromo-4-methoxyphenyl)acetamide (4.58 g. 18.8 mmol) in dimethylformamide (60 ml). The mixture was stirred at 0° C. for 30 minutes, then propargyl bromide (80% solution in toluene, 2.51 ml, 25.2 mmol) was added. The mixture was stirred at room temperature for 30 minutes, then water (150 ml) was added. The mixture was extracted with ethyl acetate (3×150 ml) and the combined organic fractions were washed water (4×150 ml) and brine (150 ml), dried (MgSO4) and evaporated under reduced pressure. The residue was dissolved in acetic acid (15 ml) and mercury (II) acetate (0.90 g, 2.8 mmol) and ammonium acetate (14.47 g, 188 mmol) were added. The mixture was heated under reflux for 4 hours, cooled and poured into water (150 ml). The pH was adjusted to 10.0 with saturated aqueous ammonia and the mixture was extracted with ethyl acetate (3×150 ml). The combined organic fractions were washed with brine (150 ml), dried (MgSO4) and evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel, eluting with CH2Cl2 /MeOH/NH3 (Aq.) (95:5:0.5) and the residue was recrystallized from ethyl acetate (30 ml)/hexane (60 ml). The solid was collected and dried in vacuo to give the title compound as a cream-coloured solid (4.98 g, 94%), 1H NMR (360 MHz, CDCl3) δ 7.48 (1H, d, J=2.6 Hz), 7.19 (1H, dd, J=8.7, 2.6 Hz), 6.95 (1H, d, J=8.7 Hz), 6.66 (1H, s), 3.95 (3H, s), 2.30 (3H, s), and 2.22 (3H, s).

Provenance & Evidence