Toluene → Tert-butyl 2-amino-3-(4-methoxyphenyl)-2-methylpropanoate

Participants

Reaction Conditions

Reaction Steps

Aldimine (2.00 g, 7.47 mmol) and O-allyl-N-benzylcinchonidinium bromide (0.38 g, 0.75 mmol, 0.10 equiv) were mixed with toluene (20 mL) at ambient temperature. The mixture was stirred for 30 min and then was cooled to 0° C. Powdered KOH (2.10 g, 37.35 mmol, 5 equiv) was added at once to convert the thin slurry into a yellow solution. The mixture was stirred for 5 min and 4-methoxybenzyl bromide (7.51 g, 37.35 mmol, 5 equiv) was added at 0 to 1° C. The solution was allowed to warm and was stirred at ambient temperature for 16 h. The reaction mixture was sequentially washed with water (20 mL) and brine (20 mL), separated, and treated with a 5-6 N HCl solution in IPA (7 mL) for 1 h at ambient temperature. The reaction mixture was washed with water (20 mL). The aqueous phase was separated and treated with toluene (20 mL). The aqueous phase was separated, treated with a 2 N NaOH solution until basic, and the product was extracted with toluene (20 mL). The toluene phase was washed with brine (20 mL), separated, and dried over Na2SO4. The solid was filtered and the solvent was stripped to dryness to afford tert-butyl 2-amino-3-(4-methoxyphenyl)-2-methylpropanoate; 1.70 g; 85.8% as a clear oil. 1H NMR (500 MHz, CDCl3): δ 7.13 (d, J=8.7 Hz, 2H, Ar), 6.81 (d, J=8.7 Hz, 2H, Ar), 3.78 (s, 3H, CH3), 3.05 (d, J=13.3 Hz, 1H, CH2), 2.71 (d, J=13.3 Hz, 1H, CH2), 1.62 (br. s, 2H, NH2), 1.45 (s, 9H, 3×CH3), 1.32 (s, 3H, CH3). 1H NMR analysis, carried out in the presence of 1.2 equiv of BINOL, resulted in 47.6% ee. Optical rotation (α25D, chloroform, c=1.38): −9.06°.

Provenance & Evidence