Sodium Hydroxide → Tert-butyl 2-((1-(4-fluorophenyl)cyclohexyl)methoxy)acetate

Participants

Reaction Conditions

Reaction Steps

A solution of (1-(4-fluorophenyl)cyclohexyl)methanol (108 mg, 521 μmol) in toluene was cooled to 0° C. and treated with a 50% aq. NaOH solution (500 μL) followed by tetrabutylammonium hydrogen sulfate (44 mg, 130 μmol). The mixture was stirred at 0° C. for 30 min and tert-butyl bromoacetate (152 mg, 781 μmol) was added. The ice bath was removed, and stirring was continued at room temperature for 2 h. The reaction mixture was diluted with EtOAc and water. The organic layer was separated, washed with water, brine, dried (Na2SO4), and concentrated. The crude oil was chromatographed on silica gel (Teledyne-Isco RediSep 12 g silica gel column) and eluted with hexanes, followed by 1% and 3% EtOAc in hexanes to obtain tert-butyl 2-((1-(4-fluorophenyl)cyclohexyl)methoxy)acetate (100 mg, 60% yield) as a colorless viscous oil. 1H NMR (400 MHz, CDCl3): δ ppm 7.28-7.46 (m, 2H), 6.92-7.09 (m, 2H), 3.78 (s, 2H), 3.39 (s, 2H), 2.09 (d, 2H), 1.67-1.86 (m, 2H), 1.47-1.59 (m, 4H), 1.44 (s, 9H), 1.31-1.38 (m, 2H).

Provenance & Evidence