Ammonium Acetate → Ethyl(+/-)-4-(1-aminobutyl)benzoate

Participants

Reaction Conditions

Reaction Steps

Sodium cyanoborohydride (29.8 g, 0.450 mol) was added to a solution of Intermediate 1 (66.1 g, 0.300 mol) and ammonium acetate (236 g, 3.00 mol) in methanol (1000 mL). The solution was fitted with a reflux condenser and heated to 60° C. for 16 h. The solution was allowed to cool to room temperature. The reaction was quenched by dropwise addition of 1N HCl (300 mL) and allowed to stir at room temperature for 1 h. The reaction mixture was concentrated to remove methanol. This mixture was diluted by careful addition of 1N NaOH (500 mL) followed by extraction with dichloromethane (3×500 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated. Purification by silica gel flash chromatography (methanol/dichloromethane) gave ethyl (+/−)-4-(1-aminobutyl)benzoate (Intermediate 2). 1H NMR (400 MHz, CDCl3) δ 8.01 (d, J=8.2 Hz, 2 H), 7.40 (d, J=8.2 Hz, 2 H), 4.38 (q, J=7.2 Hz, 2 H), 3.98 (t, J=6.9 Hz, 1 H), 1.95 (br. s., 2 H), 1.74-1.56 (m, 2 H), 1.40 (t, J=7.1 Hz, 3 H), 1.16-1.37 (m, 2 H), 0.91 (t, J=7.4 Hz, 3 H).

Provenance & Evidence