Cl.[CH2:2]([O:4][C:5](=[O:9])[CH2:6][CH2:7][NH2:8])[CH3:3].[F:10][C:11]1[CH:18]=[CH:17][C:14]([CH:15]=O)=[CH:13][CH:12]=1.C([O-])(=O)C.[Na+].C([BH3-])#N.[Na+]>CO.C(=O)(O)[O-].[Na+]>[CH2:2]([O:4][C:5](=[O:9])[CH2:6][CH2:7][NH:8][CH2:15][C:14]1[CH:17]=[CH:18][C:11]([F:10])=[CH:12][CH:13]=1)[CH3:3]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+].
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