Hydrochloric Acid → 1-(4-Hydroxyphenoxy)propan-2-one

Participants

Reaction Conditions

Reaction Steps

Methyllithium (140 ml of 1.5 molar lithium bromide complex in diethyl ether) was added to a stirred solution of 4-hydroxyphenoxyacetic acid (7.6 g) in anhydrous tetrahydrofuran (500 ml) at 0°-10° C. under argon. The reaction mixture was stirred for 40 hours at 22° C., cooled in an ice-bath and chlorotrimethylsilane (39 ml) was added over 15 minutes. The temperature was allowed to rise to 22° C. and the reaction mixture was poured into 1N hydrochloric acid (360 ml) and stirred for 30 minutes. The product was extracted into ethyl acetate (4×200 ml) and the combined extracts washed with aqueous sodium bicarbonate (2×300 ml), brine (100 ml), dried and the solvent removed under reduced pressure. The crude ketone was purified by chromatography using 31/2% tetrahydrofuran in dichloromethane as eluent. The appropriate fractions were combined and evaporated to yield 1-(4-hydroxyphenoxy)propan-2-one (2.0 g) as a white solid, m.p. 110°-112° C. (from ethyl acetate); microanalysis: found C, 65.5; H, 6.1%; required for C9H10O3 : C, 65.1; H, 6.0%. (A similar procedure for the preparation of methyl ketones is described by G. M. Rubottom and Chong-Wan Kim, J.O.C. 1983, 48, 1550-1552).

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