bis(4-fluorophenyl)methanol

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

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

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

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

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

Procedure: To 15.0 g (68.1 mmol) of 4,4'-difluorobenzhydrol was added 14.9 ml (204 mmol) of thionyl chloride in the atmosphere of argon, and the mixture was stirred at room temperature for 30 minutes. To the resulting mixture was added water followed by extraction with benzene. The organic layer was successively washed with water, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue thus obtained was subjected to column chromatography on silica gel. There was yielded 14.32 g (60 mmol) of 4,4'-difluorobenzhydryl chloride from the fraction eluted with benzene. followed by extraction with benzene The organic layer was successively washed with water dried over anhydrous sodium sulfate concentrated under reduced pressure The residue thus obtained

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

Procedure: To 5.00 g (22.7 mmol) of 4,4'-difluorobenzhydrol was added 16.5 ml (227 mmol) of thionyl chloride in the atmosphere of argon, and the mixture was stirred at room temperature for 30 minutes. To the resulting mixture was added water followed by extraction with benzene. The organic layer was successively washed with saturated sodium hydrogen carbonate solution and water, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue thus obtained was subjected to column chromatography on silica gel. There was yielded 4.90 g (20.5 mmol) of 4,4'-difluorobenzhydryl chloride from the fraction eluted with benzene. followed by extraction with benzene The organic layer was successively washed with saturated sodium hydrogen carbonate solution and water dried over anhydrous sodium sulfate concentrated under reduced pressure The residue thus obtained

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

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

Procedure: To a solution of 29,3 g of 2-chloroethanol in toluene 2 ml of concentrated sulphuric acid were added, after which 50 g of 4,4'-difluorobenzhydrol were added under stirring. The mixture was refluxed for 2 h, cooled and more toluene added. The organic phase was washed successively with water, aqueous sodium carbonate, and water and then dried. The solvent was evaporated to give 65 g of a crude product which was distilled to obtain 57.5 g (89,5%) of [1-(2-chloroethyl)]-bis-(4-fluorophenyl)methane. The mixture was refluxed for 2 h cooled The organic phase was washed successively with water, aqueous sodium carbonate, and water dried The solvent was evaporated to give 65 g of a crude product which was distilled

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

Procedure: To a solution of 29,3 g of 2-chloroethanol in toluene 2 ml of concentrated sulphuric acid were added, after which 50 g of 4,4'-difluorobenzhydrol were added under stirring. The mixture was refluxed for 2 h, cooled and more toluene added. The organic phase was washed successively with water, aqueous sodium carbonate, and water and then dried. The solvent was evaporated to give 65 g of a crude product which was distilled to obtain 57.5 g (89,5%) of [1-(2-chloroethyl)]-bis-(4-fluorophenyl)methane. The mixture was refluxed for 2 h cooled The organic phase was washed successively with water, aqueous sodium carbonate, and water dried The solvent was evaporated to give 65 g of a crude product which was distilled

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

Procedure: To a solution of 4,4'-difluorobenzhydrol (12.8 g, 58.1 mmol) and ethyl indole-2-carboxylate (10.0 g, 52.9 mmol) in 100 ml of methylene chloride was added methanesulfonic acid (3.4 ml, 52.9 mmol), followed by stirring at room temperature for one hour. Then, 4,4'-difluorobenzhydrol (1.0 g, 4.54 mmol) was further added to the reaction mixture followed by stirring for 1.5 hours to complete the reaction. A 2N aqueous sodium hydroxide solution was added to the reaction solution, and a saturated aqueous solution of ammonium chloride was further added thereto for neutralization followed by extraction with chloroform. The resulting organic layer was washed with a saturated aqueous solution of sodium bicarbonate and a saturated aqueous solution of sodium chloride, and dried over magnesium sulfate, and the solvent was distilled off under reduced pressure to give a crude product. The obtained crude product was recrystallized from ethanol to give 8.4 g (yield: 40%) of the title compound. by stirring for 1.5 hours the reaction for neutralization followed by extraction with chloroform The resulting organic layer was washed with a saturated aqueous solution of sodium bicarbonate a saturated aqueous solution of sodium chloride, and dried over magnesium sulfate the solvent was distilled off under reduced pressure to give a crude product The obtained crude product was recrystallized from ethanol

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

Procedure: To a solution of 4,4'-difluorobenzhydrol (12.8 g, 58.1 mmol) and ethyl indole-2-carboxylate (10.0 g, 52.9 mmol) in 100 ml of methylene chloride was added methanesulfonic acid (3.4 ml, 52.9 mmol), followed by stirring at room temperature for one hour. Then, 4,4'-difluorobenzhydrol (1.0 g, 4.54 mmol) was further added to the reaction mixture followed by stirring for 1.5 hours to complete the reaction. A 2N aqueous sodium hydroxide solution was added to the reaction solution, and a saturated aqueous solution of ammonium chloride was further added thereto for neutralization followed by extraction with chloroform. The resulting organic layer was washed with a saturated aqueous solution of sodium bicarbonate and a saturated aqueous solution of sodium chloride, and dried over magnesium sulfate, and the solvent was distilled off under reduced pressure to give a crude product. The obtained crude product was recrystallized from ethanol to give 8.4 g (yield: 40%) of the title compound. by stirring for 1.5 hours the reaction for neutralization followed by extraction with chloroform The resulting organic layer was washed with a saturated aqueous solution of sodium bicarbonate a saturated aqueous solution of sodium chloride, and dried over magnesium sulfate the solvent was distilled off under reduced pressure to give a crude product The obtained crude product was recrystallized from ethanol

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

Procedure: Substantially the same procedure as in Example 266 was repeated using 4,4'-difluorobenzhydrol (0.99 g, 4.50 mmol) and N-isopropylindole-2-sulfonamide (1.00 g, 4.46 mmol) to give 1.56 g (yield: 80%) of the title compound.