2,6-difluoro-4-propylphenol

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

Procedure: The crude product from b), 0.79 g of 1-fluoro-4-(trans-4-carboxycyclohexyl)cyclohex-l-ene, was cooled to 0°C. under nitrogen together with 0.66 g of 2,6-difluoro-4-propylphenol and 60 mg of dimethylaminopyridine in 10 ml of methylene chloride and treated within 45 minutes with a solution of 1.0 g of dicyclohexyl-carbodiimide in 5 ml of methylene chloride. After stirring at room temperature for 30 minutes the white suspension was filtered over a Celite/silica gel pad. The filtrate was evaporated completely and gave 1.5 g of trans-4-(1-fluoro-cyclohex- 1 -en-4-yl)cyclohexanecarboxylic acid 2,6-difluoro-4-propylphenyl ester, which gave 0.62 g of white crystals by repeated recrystallization from hexane. M.p. (C/N) 58.40°C., c.l.p. (N/I) 96.1°C. was filtered over a Celite/silica gel pad The filtrate was evaporated completely

Conditions: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into THF (85 mL), 2,6-difluoro-4-propylphenol obtained in (1-2) in Example 1 (17.2 g), 3,5-difluorobenzyl alcohol (17.2 g), triphenylphosphine (28.9 g) were dissolved, and the product was cooled to −10° C. DIAD (21.2 g) was added thereto at a rate which did not allow the internal temperature to exceed 15° C., and the product was stirred for 3 hours at room temperature. Then, 5 mL of water was added thereto, the solvent was distilled off under reduced pressure, hexane (300 mL) was added thereto, and the product was stirred. The precipitate was removed by filtration, the filtrate was washed with an aqueous solution of 50% methanol (200 mL) and a saturated salt solution in sequence, and sodium sulfate was added thereto for dehydration. The solvent was distilled off under reduced pressure, and the product was purified by silica gel column chromatography, thereby yielding a slightly yellow liquid that what 1,3-difluoro-5-[(2,6-difluoro-4-propylphenyloxy)methyl]benzene (19.1 g). were dissolved to exceed 15° C. the solvent was distilled off under reduced pressure, hexane (300 mL) was added the product was stirred The precipitate was removed by filtration the filtrate was washed with an aqueous solution of 50% methanol (200 mL) a saturated salt solution in sequence, and sodium sulfate was added The solvent was distilled off under reduced pressure the product was purified by silica gel column chromatography