1-(4-(Ethoxymethoxy)phenyl)ethanone → 2-(4-(Ethoxymethoxy)phenyl)propan-2-ol

Participants

Reaction Steps

In a 500 milliliter, three-necked oven-dried round bottom flask equipped with a magnetic stirrer and charged with 200 milliliters of 0.50 M (3,3,3-trifluoropropyl)magnesium bromide in tetrahydrofuran was added 19.4 grams (0.1 mole) of 1-(4-(ethoxymethoxy)phenyl)ethanone and the mixture was stirred at room temperature for 4 hours. The reaction was quenched by slowly pouring the mixture into 400 milliliters saturated ammonium chloride solution and extracting the product into 400 milliliters of ethyl acetate, and washing with brine then water to a neutral pH. The ethyl acetate extracts were then dried over sodium sulfate, filtered, and concentrated in the rotary evaporator affording 20.17 grams (˜96% yield) of 2-(4-(ethoxymethoxy)phenyl)propan-2-ol as an amber oil which was used without further purification. 20 grams (0.096 mole) 2-(4-(ethoxymethoxy)phenyl)propan-2-ol and 11.6 grams (0.11 mole) of triethylamine were dissolved in 40 milliliters of methylene chloride and slowly added to a flask equipped with magnetic stirrer and 11 milliliters (0.105 mole) of methacroyl chloride in 100 milliliters of dichloromethane, which had been cooled to 0° C. The resultant mixture was slowly warmed to room temperature and allowed to stir for 12 hours. Upon completion of the reaction, confirmed by thin layer chromatography, the mixture was quenched by pouring into 400 milliliters of deionized water and the product was extracted into methylene chloride. The methylene chloride extracts were then dried over sodium sulfate, filtered, and concentrated in the rotary evaporator affording 29.3 grams (˜85% yield) of 2-(4-(ethoxymethoxy)phenyl)-5,5,5-trifluoropentan-2-yl methacrylate as an amber oil. The oil was purified further by passing through a silica gel plug eluting with 70/30 hexanes/methylene chloride affording 19 grams of the pure product. 1H NMR (500 MHz, Acetone): δ 7.29-7.26 (d, 2H, 8.5 Hz), 6.98-6.95 (d, 2H, 8 Hz), 6.06 (s, 1H), 5.57 (s, 1H) 5.20 (s, 2H) 3.69-3.66 (q, 2H), 2.48-2.1 (m/m, 4H), 1.884 (s, 3H), 1.80 (s, 3H), 1.17-1.12 (t, 3H).

Provenance & Evidence