Methyl valinate hydrochloride → (S)-(-)-2-Amino-3-methyl-1,1-diphenyl-1-butanol

Participants

Reaction Steps

L-Valine methyl ester hydrochloride (9.9 g, 59.06 mmol) was added portionwise to a 1.0 M solution of phenylmagnesium bromide (108.8 g, 0.6 mol) in THF at 0° C. and heated at reflux for 20 h. After quenching with crushed ice and NH4Cl salt, the organic layer was separated, washed with brine and concentrated under reduced pressure. The resulting solid was treated with HCl (2.0 M, 100 ml) and then evaporated to dryness under reduced pressure. Impurities precipitated out as a white solid, when the amine hydrochloride salt was dissolved in hot MeOH and allowed to cool to room temperature. After removing the impurities by filtration, the filtrate was made basic with KOH (1.0 M) and the organics were extracted into diethyl ether (4×100 ml). Combined organic extracts were dried over MgSO4 and concentrated under reduced pressure to obtain a crude product as a light brown solid. Purification over silica gel, eluting with a 1:4 and 1:1 mixture of ethyl acetate and petrol gave the title compound (2) (5.42 g, 36%) as a white solid. m.p. 90–92° C. (liti 94–95° C.). [α]D25=−107.92° (c, 0.0424 in CHCl3) (litii: −127.7° (c, 0.639 in CHCl3). δH 0.81 (3H, d, 3J=6.90 Hz, CH3), 0.85 (3H, d, 3J=7.20 Hz), 1.67 (1H, ds, 3J=1.80 and 6.90 Hz, CH-Me2), 3.76 (1H, d, 3J=2.10 Hz, CH—NH2), 7.04–7.58 (10H, m, Ar). δC 16.3 and 23.2 (CH3), 28.1 (CH—Me2), 60.4 (CH—NH2), 79.9 (C—OH), 125.7, 126.1, 126.5, 126.8, 128.2 and 128.6 (o-, m- and p-Ar), 145.1 and 148.2 (α-Ar. Anal. Calcld. for C17H21NO: C 79.96; H 8.29; N 5.48. Found: C 79.80; H 8.15; N 5.39. ir 3338 (OH and NH2). m/e (CI—CH4) 256 (MH+, 14%), 72 (100%).

Provenance & Evidence