Trimethyl orthoformate → 1,1,1-Trifluoro-4-(4-hydroxyphenyl)butan-2-one

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Reaction Conditions

Reaction Steps

To a solution of 1,1,1-trifluoro-4-[4-hydroxyphenyl]-2-butanone (40.4 g, 0.185 mol) in nitromethane (300 ml) were added methanol (40 ml), trimethyl orthoformate (100 ml) and trifluoromethanesulfonic acid (1 ml). The resulting mixture was heated to 75° C. for 20 h, then cooled to r.t. and poured into sat. sodium bicarbonate (700 ml). After stirring for 10 min., the mixture was extracted with ethyl acetate (2×2 L). The combined organic layers were dried over anhydrous magnesium sulfate and concentrated in vacuo. The residue was chromatographed on silica gel (dichloromethane/methanol 98:2 to 97:3) to afford the title compound (21.5 g, 44%) as a yellow oil and 1,1,1-trifluoro-4[4-hydroxyphenyl]-2-butanone (23 g, 57%). Analytically pure sample (20.2 g, 41%) of 4-(4,4,4-trifluoro-3,3-dimethoxybut-1-yl)phenol was obtained by bulb-to-bulb distilation (98-102° C., 0.02mmHg).

Provenance & Evidence