2,2-difluoro-2-phenylacetaldehyde

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Intermediate 19 (0.88 g, 5.64 mmol) was dissolved in THF (12 mL) and (carbethoxymethylene)triphenylphosphorane (1.96 g, 5.64 mmol) was then added. The solution was stirred at 50° C. for 12 hours. The mixture was concentrated and the residue was purified by column chromatography on silica gel using n-hexane/AcOEt (5:1) as eluent. The title compound was obtained (1.10 g, 89%) as pale yellow oil. The mixture was concentrated the residue was purified by column chromatography on silica gel

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

Procedure: Obtained from Intermediate 6 (1.0 g, 6.3 mmol) by the procedure described for the Intermediate 13. The title compound was obtained (0.88 g, 86%) as oil.

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

Procedure: Obtained from Intermediate 6 (1.0 g, 6.3 mmol) by the procedure described for the Intermediate 13. The title compound was obtained (0.88 g, 86%) as oil.

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Intermediate 19 (0.88 g, 5.64 mmol) was dissolved in THF (12 mL) and (carbethoxymethylene) triphenylphosphorane (1.96 g, 5.64 mmol) was then added. The solution was stirred at 50° C. for 12 hours. The mixture was concentrated and the residue was purified by column chromatography on silica gel using n-hexane/AcOEt (5:1) as eluent. The title compound was obtained (1.10 g, 89%) as pale yellow oil. The mixture was concentrated the residue was purified by column chromatography on silica gel

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

Procedure: Obtained from Intermediate 6 (1.0 g, 6.3 mmol) by the procedure described for the Intermediate 13. The title compound was obtained (0.88 g, 86%) as oil.

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

Procedure: To a solution of oxalyl chloride (2.66 g, 21.0 mmol) in DCM (300 mL) was added DMSO (2.5 mL, 35.0 mmol) at 60° C. The mixture was stirred for 30 min. Then 2,2-difluoro-2-phenyl-ethanol (28.1 g, 18.0 mmol) was added at the same temperature. The mixture was stirred for another 30 min. Triethylamine (11.1 mL, 80.0 mmol) was added and then the mixture was stirred for 2 h at room temperature. Water was added and the organic layer was dried over anhydrous sodium sulfate and concentrated to obtain the crude product difluoro-phenyl-acetaldehyde (828 mg, 30%), which was used to the next step without further purification. The mixture was stirred for another 30 min the mixture was stirred for 2 h at room temperature the organic layer was dried over anhydrous sodium sulfate concentrated

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

Procedure: To a solution of oxalyl chloride (2.66 g, 21.0 mmol) in DCM (300 mL) was added DMSO (2.5 mL, 35.0 mmol) at 60° C. The mixture was stirred for 30 min. Then 2,2-difluoro-2-phenyl-ethanol (28.1 g, 18.0 mmol) was added at the same temperature. The mixture was stirred for another 30 min. Triethylamine (11.1 mL, 80.0 mmol) was added and then the mixture was stirred for 2 h at room temperature. Water was added and the organic layer was dried over anhydrous sodium sulfate and concentrated to obtain the crude product difluoro-phenyl-acetaldehyde (828 mg, 30%), which was used to the next step without further purification. The mixture was stirred for another 30 min the mixture was stirred for 2 h at room temperature the organic layer was dried over anhydrous sodium sulfate concentrated

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Intermediate 19 (0.88 g, 5.64 mmol) was dissolved in THF (12 mL) and (carbethoxymethylene)triphenylphosphorane (1.96 g, 5.64 mmol) was then added. The solution was stirred at 50° C. for 12 hours. The mixture was concentrated and the residue was purified by column chromatography on silica gel using n-hexane/AcOEt (5:1) as eluent. The title compound was obtained (1.10 g, 89%) as pale yellow oil. The mixture was concentrated the residue was purified by column chromatography on silica gel

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

Procedure: Obtained from Intermediate 6 (1.0 g, 6.3 mmol) by the procedure described for the Intermediate 13. The title compound was obtained (0.88 g, 86%) as oil.