4-Chlorophenol → Clofibrate

Participants

Reaction Conditions

Reaction Steps

To a solution of 4-chlorophenol (3 g, 23.3 mmol) in ethanol (100 mL) at room temperature is added potassium hydroxide (1.3 g, 23.3 mmol). The suspension is warmed at ˜35° C. for 15 min to complete dissolution before ethyl α-bromoisobutyrate (3.46 mL, 23.3 mmol) is introduced. The reaction is then heated to reflux where it is maintained for 16 h. After this time, the mixture is cooled to room temperature and filtered. The collected solids are washed with additional ethanol (10 mL) and the combined filtrates are concentrated under reduced pressure. The residue is dissolved in DCM (60 mL) and washed with water (×2). The organic phase is dried (Na2SO4), filtered and concentrated under reduced pressure to provide the title compound as a clear colourless liquid (2.30 g, 40%). 1H NMR (400 MHz, CHLOROFORM-d): δ ppm 1.25 (3H, t, J=7.1 Hz), 1.58 (6H, s), 4.23 (2H, q, J=7.1 Hz), 6.78 (2H, d, J=9.0 Hz), 7.19 (2H, d, J=9.1 Hz); m/z: 243/245 [M+H+].

Provenance & Evidence