Potassium Carbonate → 2-{2-[2-Methyl-3-(4-trifluoromethyl-phenyl)-benzo[b]thiophen-6-yloxy]-ethoxy}-tetrahydro-pyran

Participants

Reaction Conditions

Reaction Steps

4.0 g (13.0 mmol) 2-Methyl-3-(4-trifluoromethyl-phenyl)-benzo[b]thiophen-6-ol (example 26.5) dissolved in 30 ml N,N-dimethylformamide were treated with 2.69 g (19.5 mmol, 1.5 eq) K2CO3 and 3.06 ml (19.5 mmol, 1.5 eq) 2-(2-Bromo-ethoxy)-tetrahydro-pyran. The reaction mixture was stirred at 120° C. for 3 hours, cooled to room temperature, poured into 100 ml of ice-water and extracted 3 times with 50 ml of ether. The combined ether phases were washed with brine, dried over magnesium sulfate and evaporated under reduced pressure. The residue formed was filtered over silica gel with dichloromethane as the eluent giving 5.76 g crude 2-{2-[2-Methyl-3-(4-trifluoromethyl-phenyl)-benzo[b]thiophen-6-yloxy]-ethoxy}-tetrahydro-pyran. This crude product was subsequently dissolved in 70 ml of 2N HCl in methanol and the reaction mixture stirred for 1 hour at room temperature. Subsequently, it was poured into a diluted sodium hydroxide/ice solution and extracted 3 times with 150 ml of dichloromethane. The combined dichloromethane phases were washed with brine, dried over magnesium sulfate and evaporated under reduced pressure. The residue formed was chromatographed on silica gel with dichloromethane as the eluent giving 4.3 g (93%) 2-[2-Methyl-3-(4-trifluoromethyl-phenyl)-benzo[b]thiophen-6-yloxy]-ethanol as colorless solid, MS: 352 (M+).

Provenance & Evidence