Sodium Methoxide → 4-Fluoro-2-(methoxymethyl)benzonitrile

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Reaction Steps

A solution of 2-(bromomethyl)-4-fluorobenzonitrile (501 mg, 2.3 mmol) in methanol (5 mL) was treated with sodium methoxide (5.6 mL of 0.5 M solution in methanol, 2.81 mmol) and stirred for 1 hour at room temperature then heated to 55° C. for 2 hours. The mixture was cooled to room temperature, condensed to dryness and directly purified by normal phase flash column chromatography on a 20 g silica gel column (5-60% ethyl acetate/hexanes gradient). Pure fractions were pooled and concentrated in vacuo to yield 4-fluoro-2-(methoxymethyl)benzonitrile (110 mg, 0.66 mmol, 28% yield) as an oil. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.97 (dd, J=8.46, 5.50 Hz, 1H), 7.46 (dd, J=9.53, 2.55 Hz, 1H), 7.39 (td, J=8.59, 2.69 Hz, 1H), 4.58 (s, 2H), 3.37 (s, 3H).

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