4-Fluorobenzaldehyde → Ethyl 3-{[(4-fluorophenyl)methyl]amino}propanoate

Participants

Reaction Conditions

Reaction Steps

A suspension of β-alanine ethyl ester hydrochloride salt (2.0 g, 13.0 mmol), 4-fluorobenzaldehyde (1.61 g, 13.0 mmol), sodium acetate (2.13 g, 26.0 mmol), and 4 Å molecular sieves (0.5 g/mmol) in methanol (50 mL) was treated with sodium cyanoborohydride (1.63 g, 26.0 mmol). The reaction was stirred at 25° C. for 4 h, diluted with a saturated aqueous sodium bicarbonate solution (150 mL), and extracted with ethyl acetate (3×50 mL). The combined organic layers were dried over magnesium sulfate, filtered, and concentrated in vacuo. The crude oil was purified by flash column chromatography (ISCO RediSep column, 20 to 70% ethyl acetate in hexanes) to give 3-(4-fluoro-benzylamino)-propionic acid ethyl ester (2.08 g, 71%) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ: 1.26 (t, 3H, J=7.0 Hz), 2.52 (t, 2H, J=6.5 Hz), 2.88 (t, 2H, J=6.2 Hz), 3.76 (s, 2H), 4.14 (q, 2H, J=6.8 Hz), 6.96-7.01 (m, 2H), 7.26-7.28 (m, 2H). LC-MS (ESI) calculated for C12H11FNO2: 225.3, found 226.2 [M+H+].

Provenance & Evidence