Methanol → 2-(3-Chloro-4-methoxyphenyl)acetonitrile

Participants

Reaction Steps

To a suspension of t-BuOK (4.8 g, 40 mmol) in THF (30 mL) was added a solution of TosMIC (3.9 g, 20 mmol) in THF (10 mL) at −78° C. and the mixture was stirred for 10 minutes. A solution of 3-chloro-4-methoxy-benzaldehyde (1.7 g, 10 mmol) in THF (10 mL) was added dropwise, and the reaction was stirred at −78° C. for 1.5 hours. To the cooled reaction mixture was added methanol (10 mL) and the mixture was heated at reflux for 30 minutes. The solvent were evaporated to give a crude residue that was dissolved in water (20 mL). The aqueous phase was extracted with ethyl acetate (20 mL×3). The combined organic layers were dried and evaporated under reduced pressure to give a crude product that was purified by column chromatography (petroleum ether/ethyl acetate 10:1) to yield 2-(3-chloro-4-methoxyphenyl)acetonitrile (1.5 g, 83%). 1H NMR (400 MHz, CDCl3) δ 7.33 (d, J=2.4 Hz, 1H), 7.20 (dd, J=2.4, 8.4 Hz, 1H), 6.92 (d, J=8.4 Hz, 1H), 3.91 (s, 3H), 3.68 (s, 2H). 13C NMR (100 MHz, CDCl3) δ 154.8, 129.8, 127.3, 123.0, 122.7, 117.60, 112.4, 56.2, 22.4.

Provenance & Evidence