4-Fluorobenzaldehyde → Rac-3-(4-fluoro-benzylamino)-2-methyl-propionic acid ethyl ester

Participants

Reaction Conditions

Reaction Steps

4-Fluorobenzaldehyde (0.622 mL, 5.80 mmol), sodium acetate (0.951 g, 11.6 mmol), powdered/activated 4 Å molecular sieves (2.0 g) and sodium cyanoborohydride (0.729 g, 11.6 mmol) were added sequentially to a solution of racemic 3-amino-2-methyl-propionic acid ethyl ester hydrochloride (0.972 g, 5.80 mmol) in methanol (30 mL) at 25° C. The mixture was stirred at 25° C. for 20 h, and then was filtered through Celite. The Celite was washed with methanol (2×30 mL) and the combined filtrate and washings were concentrated in vacuo. The residue was partitioned between half-saturated aqueous sodium bicarbonate solution (150 mL) and ethyl acetate (2×150 mL). The combined organic layers were dried over sodium sulfate and were concentrated in vacuo. The residue was purified by flash column chromatography (Teledyne Isco RediSep column; 0-80% ethyl acetate in hexanes) to afford rac-3-(4-fluoro-benzylamino)-2-methyl-propionic acid ethyl ester (0.821 g, 3.43 mmol, 59%) as a pale yellow oil. 1H NMR (400 MHz, CDCl3) δ: 1.18 (3H, d, J=7.2 Hz), 1.26 (3H, t, J=6.9 Hz), 2.63-2.72 (2H, m), 2.84-2.91 (1H, m), 3.75 (1H, d, J=13.3 Hz), 3.79 (1H, d, J=13.4 Hz), 4.14 (2H, q, J=6.9 Hz), 6.97-7.01 (2H, m), 7.25-7.29 (2H, m).

Provenance & Evidence