4'-METHYL-3'-(TRIFLUOROMETHYL)ACETOPHENONE synthesis

Yield:851262-98-1 77%

Reaction Conditions:

Stage #1: diethyl malonatewith potassium tert-butylate in dimethyl sulfoxide at 0 - 20; for 0.333333 h;
Stage #2: 1-(4-fluoro-3-(trifluoromethyl)phenyl)ethanone in dimethyl sulfoxide at 20 - 60; for 22 h;
Stage #3: with potassium hydroxide in water;dimethyl sulfoxide at 0 - 100; for 23 h;

Steps:

A.1

Example A.1 4-Methyl-3-trifluoromethyl-acetophenone To a stirred and cooled (0° C.) solution of potassium tert.-butanolate (1.39 g, 12 mmol) in DMSO (3 ml) was added diethyl malonate (1.9 ml, 12 mmol) and the reaction mixture was stirred for 20 min at room temperature. To the white suspension was added at room temperature 4-fluoro-3-trifluoromethyl-acetophenone (1 g, 5 mmol) and DMSO (2 ml). The reaction mixture was stirred for 6 h at 60° C. and for 16 h at room temperature. The reaction mixture was cooled (0° C.), a solution of potassium hydroxide (1.09 g, 19 mmol) in water (2 ml) was added and the mixture was stirred at 100° C. for 23 h. The mixture was poured into ice/water (40 ml) and extracted with diethyl ether (2*40 ml). The combined organic layers were washed with water (3*30 ml), brine (30 ml), dried (MgSO₄) and evaporated. The crude product (0.92 g) was further purified by column chromatography on silica gel (heptane/ethyl acetate 3:1) to give the title compound (0.76 g, 77%) as a light yellow liquid. MS (EI) 202.0 [M].

References:

US2006/183756,2006,A1 Location in patent:Page/Page column 9-10