Sodium Chloride → HCID 178490609, compound

Participants

Reaction Conditions

Reaction Steps

Under an atmosphere of nitrogen, 3-benzyloxy-4-methoxybenzyl magnesium chloride is prepared from 3-benzyloxy-4-methoxybenzylchloride (C. Schopf and L. Winterhalder, Ann. 544, 62 (1940) (22.0 g, 84 mmol) and magnesium turnings (4.1 g) in tetrahydrofuran (THF) (100 ml) at room temperature (about 2 hours). After cooling to -30° C., a solution of fluoroacetonitrile (4.94 g) in THF (40 ml) is added dropwise, maintaining the temperature between -30° C. and -40° C. Stirring is continued at this temperature for another 30 minutes, then the mixture is poured into a solution of sodium cyanide (12.3 g) and ammonium chloride (17.9 g) in water (150 ml), previously cooled with ice. After stirring for 30 minutes, the mixture is saturated with sodium chloride whereupon the phases separate. After extracting the aqueous phase two more times with diethyl ether, the combined THF and ether phases are dried (Na2SO4) and evaporated to give the crude aminonitrile (25.9 g) as a brown oil. The oil is dissolved in ether and treated with HCl gas to prepare the hydrochloride as an oil. This oil is recrystallized twice from ethanol/ether to give 2-fluoromethyl-2-amino-3-(3'-benzyloxy-4'-methoxyphenyl)propionitrile as the hydrochloride as a slightly colored solid; NMR (CD3OC): 3.47 ppm (3H, s), 4.32 ppm (2H, d, JH--F =46 Hz), 4.73 ppm (2H, s), 6.60 ppm (3H, m), 6.97 ppm (5H, m).

Provenance & Evidence