4-Ethoxy-3-fluorophenol

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1-Iodomethyl-4-(4-pentylcyclohexyl)cyclohexane (9.8 g, 26 mmol) was reacted with 4-ethoxy-3-fluorophenol (3.7 g, 24 mmol) in THF (60 ml) in the presence of NaH (ca. 24 mmol) used as a base. After treatment was carried out by the same method as in Example 3 to obtain 1-ethoxy-2-fluoro-4-(4-(4-pentylcyclohexyl)cyclohexyl)methyloxybenzene (yield: 39%).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 22.3 g of the crude 3-fluoro-4-ethoxyphenyl boronic acid obtained in the first step was dissolved in 200 ml of tetrahydrofuran, and 23.6 g (208 mmol) of aqueous 30% hydrogen peroxide was added while being kept at about 35° C. in a warm bath. After addition and after stirring the reaction solution at a room temperature for 24 hours, the reaction solution was poured into 300 ml of water, then sodium hydrogen sulfite was added and stirred at a room temperature for one hour. The reaction solution was extracted with 300 ml of ethyl acetate and the extracted layer was washed with water and then with an aqueous saturated sodium chloride solution successively and, after dying over anhydrous magnesium sulfate, concentrated under a reduced pressure. The concentrated residue was purified by silica gel column chromatography using a ethyl acetate/heptane mixed solvent as an eluent to obtain 17.6 g (113 mmol) of 3-fluoro-4-ethoxyphenol. while being kept at about 35° C. in a warm bath After addition stirred at a room temperature for one hour The reaction solution was extracted with 300 ml of ethyl acetate the extracted layer was washed with water concentrated under a reduced pressure The concentrated residue was purified by silica gel column chromatography