5-chloro-2-(2,2,2-trifluoroethoxy)benzaldehyde

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: Under a nitrogen atmosphere, in a round-bottom flask equipped with a reflux condenser were placed 400 mg (1.7 mmol) of the above nitrile and 10 ml of formic acid. To the system were added ca. 500 mg of Raney nickel and the mixture was heated at ref lux for 6 hours and stirred at room temperature overnight. The mixture was filtered through a pad of a diatomaceous earth, and the pad was rinsed with water and CHCl3. The layers were separated and the aqueous phase was extracted with three portions of CHCl3. The combined organic fractions were dried and concentrated to obtain 270 mg of the title compound. Under a nitrogen atmosphere, in a round-bottom flask equipped with a reflux condenser the mixture was heated at ref lux for 6 hours The mixture was filtered through a pad of a diatomaceous earth the pad was rinsed with water and CHCl3 The layers were separated the aqueous phase was extracted with three portions of CHCl3 The combined organic fractions were dried concentrated

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

Procedure: Under a nitrogen atmosphere, in a round-bottom flask equipped with a reflux condenser were placed 400 mg (1.7 mmol) of the above nitrile and 10 ml of formic acid. To the system were added ca. 500 mg of Raney nickel and the mixture was heated at ref lux for 6 hours and stirred at room temperature overnight. The mixture was filtered through a pad of a diatomaceous earth, and the pad was rinsed with water and CHCl3. The layers were separated and the aqueous phase was extracted with three portions of CHCl3. The combined organic fractions were dried and concentrated to obtain 270 mg of the title compound. Under a nitrogen atmosphere, in a round-bottom flask equipped with a reflux condenser the mixture was heated at ref lux for 6 hours The mixture was filtered through a pad of a diatomaceous earth the pad was rinsed with water and CHCl3 The layers were separated the aqueous phase was extracted with three portions of CHCl3 The combined organic fractions were dried concentrated

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: Sodium borohydride (200 mg, 5.3 mmol) was added to a solution of 2-(2,2,2-trifluoroethoxy)-5-chlorobenzaldehyde (2 g, 8.4 mmol) in ethanol at room temperature. After stirring for 1 hr, the solvent was removed under reduced pressure. Aqueous ammonium chloride was added to the residue to destroy excess hydride following which the mixture was extracted with ethyl acetate. The organic extracts were washed with brine and then dried over sodium sulfate. Concentration yielded the title compound as an oil: 1H NMR (CDCl3) δ7.41 (d, J=2.4 Hz, 1H), 7.25 (m, 1H), 6.77 (d, J=8.8 Hz, 1H), 4.73 (d, J=4.6 Hz, 2H), 4.40 (m, 2H). the solvent was removed under reduced pressure Aqueous ammonium chloride was added to the residue to destroy excess hydride following which the mixture was extracted with ethyl acetate The organic extracts were washed with brine dried over sodium sulfate Concentration

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

Procedure: Using a small volume of DMF, the trifluorethoxy triflate thus prepared was added to a mixture of 5-chlorosalicylaldehyde (5 g, 32 mmol) and cesium carbonate (21 g, 64 mmol) in DMF (50 mL) at room temperature. After stirring at room temperature overnight the solids were filtered off and the filtrate concentrated under reduced pressure. The residue was diluted with ether and washed well with water. Drying (Na2SO4) and concentration yielded the title compound as an oil: 1H NMR (CDCl3) δ10.42 (s, 1H), 7.84 (dd, J=2.6 Hz, 1H), 7.54 (m, 1H), 6.93 (d, J=8.8 Hz, 1H), 4.48 (qd, J=1.5, 7.8 Hz, 2H). were filtered off the filtrate concentrated under reduced pressure The residue was diluted with ether washed well with water Drying (Na2SO4) and concentration

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 5-Chloro-2-(2,2,2-trifluoro-ethoxy)-benzaldehyde (4 g, 16 mmol) and 6-chlorooxindole (2.8 g, 16 mmol) were mixed in anhydrous methanol (20 mL). Then pyrrolidine (1.32 mL, 16 mmol) was added slowly at r.t. The mixture was heated to 70° C. for 3 h and cooled to room temperature. The precipitate was collected by filtration to give title compound as a yellow solid (Yield: 4.45 g, 72%). cooled to room temperature The precipitate was collected by filtration

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

Procedure: 5-Chloro-2-hydroxy-benzaldehyde (3.1 g, 2 mmol), 1,1,1-trifluoro-2-iodo-ethane (2.4 mL, 24 mmol), K2CO3 (5.5 g, 40 mmol) and KI (0.1 g) were mixed in DMF (20 mL). Then the mixture was irradiated under microwave at 180° C. for 1 h. The mixture was filtered and the filtrate was concentrated. The residue was dissolved in ethyl acetate and washed with 1N NaOH. Then the organic layer was separated, dried over anhydrous Na2SO4 and concentrated to give title compound as a yellow solid (Yield: 4 g). Then the mixture was irradiated under microwave at 180° C. for 1 h The mixture was filtered the filtrate was concentrated The residue was dissolved in ethyl acetate washed with 1N NaOH Then the organic layer was separated dried over anhydrous Na2SO4 concentrated

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

Procedure: Under a nitrogen atmosphere, in a round-bottom flask equipped with a refluxcondenser were placed 400 mg (1.7 mmol) of the above nitrile and 10 ml of formic acid. To the system were added ca. 500 mg of Raney nickel and the mixture was heated at reflux for 6 hours and stirred at room temperature overnight. The mixture was filtered through a pad of a diatomaceous earth,and the pad was rinsed with water and CHCl3. The layers were separatedand the aqueous phase was extracted with three portions of CHCl3. The combined organic fractions were dried and concentrated to obtain 270 mg ofthe title compound. Under a nitrogen atmosphere, in a round-bottom flask equipped with a refluxcondenser the mixture was heated at reflux for 6 hours The mixture was filtered through a pad of a diatomaceous earth,and the pad was rinsed with water and CHCl3 was extracted with three portions of CHCl3 The combined organic fractions were dried concentrated