1-HYDROXY-4-BUTOXY-2,3-DIFLUOROBENZENE

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Butoxy-2,3-difluorophenol (24) (4.6 g) and tripotassium phosphate (K3PO4) (14.0 g) were added to DMF (100 ml) under a nitrogen atmosphere, and the stirring was continued at 70° C. The compound (20) (3.0 g) was added thereto, and the stirring was continued at 70° C. for 7 hours. After the reaction mixture obtained had been cooled to 30° C. and separated from solid materials by filtration, toluene (100 ml) and water (100 ml) were added thereto, and mixed. The mixture was then allowed to separate into organic and aqueous phases, and the extraction into an organic phase was carried out. The organic phase obtained was washed with brine and dried over anhydrous magnesium sulfate. Then, the solvent was distilled off, and the residue obtained was purified by means of column chromatography (silica gel; heptane/toluene=1/2 by volume). The product was further purified by means of recrystallization (Solmix A-11: heptane=1:2 by volume), giving 4.02 g of 2,3-difluoro-4-ethoxy-[trans-4-(2,3-difluoro-4-butoxyphenoxymethyl)cyclohexyl]benzene (No. 831). The yield based on the compound (20) was 85.1%. was continued at 70° C After the reaction mixture obtained separated from solid materials by filtration, toluene (100 ml) and water (100 ml) were added mixed to separate into organic and aqueous phases the extraction into an organic phase The organic phase obtained was washed with brine dried over anhydrous magnesium sulfate Then, the solvent was distilled off the residue obtained was purified by means of column chromatography (silica gel; heptane/toluene=1/2 by volume) The product was further purified by means of recrystallization (Solmix A-11: heptane=1:2 by volume)

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

Procedure: The compound (23) (40.0 g) and acetic acid (100 ml) were put in a reaction vessel under a nitrogen atmosphere, and hydrogen peroxide (31% aqueous solution; 40.4 ml) was added dropwise in the temperature range of 25° C. to 30° C., and the stirring was continued for another 2 hours. Then the reaction mixture was poured into a vessel containing sodium hydrogen sulfite solution (100 ml) and ethyl acetate (300 ml), and mixed. Then the mixture was allowed to separate into organic and aqueous phases, and the extraction was carried out. The organic phase obtained was washed sequentially with water and brine, and dried over anhydrous magnesium sulfate. Then the solvent was distilled off under reduced pressure, giving 31.7 g of 4-butoxy-2,3-difluorophenol (24). The yield based on the compound (23) was 90.2%. Then the reaction mixture was poured into a vessel mixed to separate into organic and aqueous phases the extraction The organic phase obtained was washed sequentially with water and brine dried over anhydrous magnesium sulfate Then the solvent was distilled off under reduced pressure

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

Procedure: 0.1 mol of 2,3-difluoro-4-butoxyphenol, 0.11 mol of trans-4-pentylcyclohexylmethyl bromide and 0.11 mol of potassium carbonate are heated at 100° in 100 ml of dimethylformamide (DMF) for 16 hours. After cooling, the inorganic salts are filtered off with suction, the filtrate is concentrated and water is added. Extraction with methylene chloride gives 1-butoxy-2,3-difluoro-4-(trans-4-pentylcyclohexylmethoxy)benzene. After cooling the inorganic salts are filtered off with suction the filtrate is concentrated water is added Extraction with methylene chloride