Under nitrogen protection, 132 g of crude 1-(1-hydroxy-4-propylcyclohexyl)-3,5-difluorobenzene was dissolved with 2.99 g of p-toluenesulfonic acid monohydrate in 250 mL of toluene. The reaction mixture was heated and refluxed and stirred for 2 hours while the water generated was removed via a water separator. Upon completion of the reaction, the solution was cooled to room temperature and the organic layer was washed with saturated aqueous sodium bicarbonate and saturated saline in turn. The organic layer was dried over anhydrous sodium sulfate and the solvent was removed by distillation under reduced pressure. The residue was completely dissolved in 280 mL of ethyl acetate, and 7.1 g of 5% palladium/carbon catalyst was added, and the reaction was stirred under hydrogen atmosphere (5 MPa pressure) for 6 hours. At the end of the reaction, the palladium catalyst was removed by filtration and the filtrate was distilled under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography. The purified product was dissolved with 3.39 g of potassium tert-butoxide in 350 mL of DMF and the reaction was stirred at room temperature for 4 hours. After the reaction was completed, water and hexane were added for liquid-liquid separation. The aqueous layer was extracted with hexane, the organic layer and hexane extract were combined and washed with saturated saline. The organic layer was dried over anhydrous sodium sulfate and then distilled under reduced pressure to remove the solvent and further distilled at 206 Pa pressure (boiling point 110 °C to 112 °C) to give 58.05 g of 1-(trans-4-propylcyclohexyl)-3,5-difluorobenzene.
