2-(Methyloxy)-4-(2-oxoethyl)benzonitrile → 4-(2-Hydroxypropyl)-2-methoxybenzonitrile

Reaction equation

[CH3:1][O:2][C:3]1[CH:10]=[C:9]([CH2:11][CH:12]=[O:13])[CH:8]=[CH:7][C:4]=1[C:5]#[N:6].[CH3:14][Mg]Br>ClCCl.C1COCC1>[OH:13][CH:12]([CH3:14])[CH2:11][C:9]1[CH:8]=[CH:7][C:4]([C:5]#[N:6])=[C:3]([O:2][CH3:1])[CH:10]=1

Participants

Procedure

To a stirred solution of 2-methoxy-4-(2-oxoethyl)benzonitrile (1.5 g, 8.5 mmol) in dichloromethane (30 mL) at 0° C. was added 2.8 mL (8.5 mmol) of a 3.0 M solution of methylmagnesium bromide in THF. The reaction mixture was allowed to warm up to rt and stirred for 12 h. The reaction was then quenched by the addition of 10 mL of 1 N hydrochloric acid and extracted with dichloromethane (2×30 mL). The combined organic extracts were dried with magnesium sulfate, filtered, and concentrated in vacuo. The crude residue was purified on silica (30% EtOAc/hexanes as eluent) to afford 4-(2-hydroxypropyl)-2-methoxybenzonitrile. 1H NMR (500 MHz, CDCl3) δ 7.47 (d, 1H, J=7.8 Hz), 6.85 (dd, 1H, J=3.4 Hz), 6.82 (s, 1H), 4.05 (m, 1H), 3.93 (d, 2H), 3.91 (s, 3H), 1.25 (d, 2H, J=6.1 Hz); LCMS: [(M+1)]+=192.30; tR=2.39 min.