1-fluoro-2-(trifluoromethoxy)benzene

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

Procedure: Dimethoxyethane (15 ml) was added to the above 3-(4-(2-(3-fluoro-4-trifluoromethoxyphenyl)ethyl)cyclohexyl)propanol (1.52 g, 4.4 mmol), followed by-dropwise adding DAST (1.40 g, 8.7 mmol), refluxing the mixture for 5 hours, extracting the resulting product with toluene, washing the organic layer successively with a saturated aqueous solution of sodium bicarbonate and water, drying over MgSO4, distilling off the solvent, purifying the residue according to column chromatography treatment using heptane as a developing solvent, on silica gel, distilling off the solvent, and recrystallizing the residue from ethanol, to isolate 1-(3-fluoropropyl)cyclohexyl)-3-fluoro-4-trifluoromethoxybenzene (0.12 g, 0.34 mmol). Yield: 7.7%. Its clearing point measured by PERKIN-ELMER 7 series Thermal Analysis System was -5.89° C. refluxing the mixture for 5 hours extracting the resulting product with toluene washing the organic layer successively with a saturated aqueous solution of sodium bicarbonate and water drying over MgSO4 distilling off the solvent purifying the residue on silica gel, distilling off the solvent recrystallizing the residue from ethanol

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 1-fluoro-2-(trifluoromethoxy)benzene [2106-18-5] (20.0 g, 111 mmol) in dry THF (200 mL), cooled to −78° C., was added dropwise n-BuLi (2.5 M solution in n-hexane; 65 mL, 160 mmol) and subsequently TMEDA (60 mL). The reaction mixture was stirred for additional 60 min at −78° C., followed by addition of a solution of iodine (30.2 g, 120 mmol) in dry THF (50 mL). The resulting mixture was stirred for 1 h and then quenched by addition of a saturated aqueous NH4Cl solution (20 mL). The organic layer was washed with 1N HCl, water and brine, and dried over MgSO4. Volatiles were removed in vacuo to afford the title compound as yellow oil. The product was used in the next reaction step without further purification. MS (LC/MS): 306.0 [M+H]+. The resulting mixture was stirred for 1 h quenched by addition of a saturated aqueous NH4Cl solution (20 mL) The organic layer was washed with 1N HCl, water and brine dried over MgSO4 Volatiles were removed in vacuo