4-Fluorobenzaldehyde → Rac-3-(4-fluoro-benzylamino)-hexanoic acid ethyl ester

Participants

Reaction Conditions

Reaction Steps

4-Fluorobenzaldehyde (0.287 mL, 2.68 mmol), sodium acetate (0.439 g, 5.35 mmol), powdered/activated 4 Å molecular sieves (0.72 g) and sodium cyanoborohydride (0.336 g, 5.35 mmol) were added sequentially to a solution of racemic 3-amino-hexanoic acid ethyl ester hydrochloride (0.524 g, 2.68 mmol) in methanol (10 mL) at 25° C. The mixture was stirred at 25° C. for 2 h, and then was filtered through Celite. The Celite was washed with ethyl acetate (2×30 mL) and the combined filtrate and washings were 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; 10-80% ethyl acetate in hexanes) to afford rac-3-(4-fluoro-benzylamino)-hexanoic acid ethyl ester (0.43 g, 1.61 mmol, 60%) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ: 0.92 (3H, t, J=7.4 Hz), 1.26 (3H, t, J=7.1 Hz), 1.32-1.43 (2H, m), 1.45-1.52 (1H, m), 1.53-1.62 (1H, m), 2.51 (2H, d, J=6.3 Hz), 3.03-3.09 (1H, m), 3.77-3.84 (2H, m), 4.14 (2H, q, J=7.1 Hz), 6.97-7.02 (2H, m), 7.31-7.34 (2H, m).

Provenance & Evidence