Lithium borohydride → 5-Fluoro-4-(2-hydroxyethyl)-2-methoxybenzonitrile

Reaction equation

C[O:2][C:3](=O)[CH2:4][C:5]1[CH:10]=[C:9]([O:11][CH3:12])[C:8]([C:13]#[N:14])=[CH:7][C:6]=1[F:15].[BH4-].[Li+]>C1COCC1.[Cl-].[NH4+]>[F:15][C:6]1[C:5]([CH2:4][CH2:3][OH:2])=[CH:10][C:9]([O:11][CH3:12])=[C:8]([CH:7]=1)[C:13]#[N:14]

Participants

Procedure

To a solution of methyl(4-Cyano-2-fluoro-5-methoxyphenyl)acetate (5.0 g, 22 mmol) in THF (50 mL) at 0° C. was added lithium borohydride (14.6 mL, 29.1 mmol). The reaction was stirred for 12 h, then was diluted with saturated ammonium chloride solution and extracted three times with ethyl acetate. The combined organic layers were washed with brine, dried (Na2SO4), filtered, and concentrated. Silica gel column chromatography (50→100% EtOAc:hex.) provided 5-fluoro-4-(2-hydroxyethyl)-2-methoxybenzonitrile. 1H NMR (500 MHz, CD3OD) δ 7.19 (d, J=5.3 Hz, 1H), 6.89 (d, J=5.4 Hz, 1H), 4.21 (br s, 1H), 3.88 (s, 3H), 3.82 (m, 2H), 2.92 (m, 2H); LC/MS: [(M+1)]+=196.2; tR=0.58 min.