3-Fluoroanisole → 2-Fluoro-4-methoxybenzonitrile

Temperature

60 °C

A stirred solution of 3-fluoroanisole (7.0 g, 50.3 mmol) in 50 mL of chloroform is treated with bromine (2.59 mL, 50.3 mmol) over 30 minutes at room temperature. The reaction is heated to 60° C. for 7 hours and concentrated in vacuo. The resulting material is dissolved in 10 mL of N,N-dimethylformamide and treated with copper cyanide (5.9 g, 65.39 mmol). After refluxing overnight, the reaction is partitioned between ethyl acetate and acidic ferric chloride solution (a mixture of 19.2 g of ferric chloride hexahydrate, 44.8 mL of hydrochloric acid, and 48 mL of water). The organic phase is washed with brine, dried over magnesium sulfate, and concentrated in vacuo. The resulting material is purified by chromatography on silica gel (210 g) with 10% ethyl acetate/hexane as the eluent to afford 2-fluoro-4-methoxy-benzonitrile.

1. concentrationconcentrated in vacuo
2. dissolutionThe resulting material is dissolved in 10 mL of N,N-dimethylformamide
3. temperatureAfter refluxing overnight
4. customthe reaction is partitioned between ethyl acetate and acidic ferric chloride solution (
5. additiona mixture of 19.2 g of ferric chloride hexahydrate, 44.8 mL of hydrochloric acid, and 48 mL of water)
6. washThe organic phase is washed with brine
7. dry with materialdried over magnesium sulfate
8. concentrationconcentrated in vacuo
9. customThe resulting material is purified by chromatography on silica gel (210 g) with 10% ethyl acetate/hexane as the eluent

ORD record

ord-ffe8dc77bfae4810bc1b73e588526228

Source dataset

uspto-grants-1995_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05455274