4-Methoxybenzaldehyde → (2R)-2-(4-Methoxybenzylamino)-4-methylpentanoic acid amide

Participants

Reaction Steps

A solution of D-leucinamide hydrochloride (2.8 g, 16.8 mmol), and p-anisaldehyde (2.29 g, 16.8 mmol) in methanol (150 mL) was treated with anhydrous ZnCl2 (538 mg, 5 mmol). The resulting suspension was then treated with NaCNBH3 (1.05 g, 16.8 mmol) portion wise and heated at reflux for 3 h. The reaction was cooled to rt, quenched with saturated NaHCO3 (3 mL), diluted with EtOAc (500 mL), and washed with brine. Concentration afforded the crude benzyl amine as a white wax, which was carried on without further purification (3.57 g, 84%). MS (ESI), (M+H)+ 251.4; 1H NMR (CDCl3) δ 7.20 (d, 2H, J=6.6), 7.10 (br s, 2H), 6.88 (d, 2H, J=8.4), 5.30 (br s, 1H), 3.80 (s, 3H), 3.63 (dd, 2H, J=4.5, 12), 1.44-1.65 (m, 3H), 0.95 (d, 3H, J=6.3), 0.80 (d, 3H, J=6.3).

Provenance & Evidence