4,4,4-trifluoro-2-(2,2,2-trifluoroethyl)butan-1-ol

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:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 4,4,4-trifluoro-2-(2,2,2-trifluoroethyl)butan-1-ol (1.5 g, 7.14 mmol) in CH2Cl2 saturated with water (30 mL) was stirred under nitrogen at 0° C. Dess-Martin periodinane reagent (6.35 g, 14.99 mmol) was added in one portion. The resulting suspension was stirred at 25° C., monitoring the progress of reaction by TLC analysis (1:2 EtOAc/hexane). As the rate of conversion of the starting material slowed, additional 2 mL portions of CH2Cl2 saturated with water were added (three portions over 15 min). After 19 h at 25° C., the reaction was complete by TLC. The solution was diluted with Et2O (50 mL) and a solution of sodium thiosulfate, Na2S2O3 (73.33 mmol, 11.6 g, 11 eq) in 80% saturated aqueous sodium bicarbonate solution (50 mL) was added. The mixture was stirred rapidly for 10 min until both phases were clear. The layers were separated and the aqueous phase was extracted with ether (30 mL). The combined organic layers were washed sequentially with saturated aqueous sodium bicarbonate (10 mL) and brine (15 mL), then dried over MgSO4, filtered and concentrated to 50% of its original volume to give 4,4,4-trifluoro-2-(2,2,2-trifluoro-ethyl)-butyraldehyde as a solution (20 mL). Mass Spectrum (+ESI): (M+H)+. The mixture was stirred rapidly for 10 min until both phases The layers were separated the aqueous phase was extracted with ether (30 mL) The combined organic layers were washed sequentially with saturated aqueous sodium bicarbonate (10 mL) and brine (15 mL) dried over MgSO4 filtered concentrated to 50% of its original volume

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

Procedure: To a suspension of LAH (1.0 g) in Et2O (100 mL) at 25° C. was added slowly 4,4,4-trifluoro-2-(2,2,2-trifluoroethyl)-butyric acid ethyl ester (5.0 g, 19.8 mmol). The resulting mixture was stirred at reflux for 4 h. The cooled reaction mixture was quenched sequentially with water (1.0 mL), 15% NaOH in water (1.0 mL) and water (3.0 mL). After the resulting mixture was allowed to stir at 25° C. for 17 h, Na2SO4 (20 g) was added and stirring at 25° C. continued for 1 h. The resulting suspension was filtered through a pad of the Celite® reagent and Na2SO4. The filtrate was distilled to remove all solvents to afford the desired product as a colorless liquid (1.7 g, 41%). Mass Spectrum (−ESI): 269 [M+OAc]− at reflux for 4 h The cooled reaction mixture was quenched sequentially with water (1.0 mL), 15% NaOH in water (1.0 mL) and water (3.0 mL) to stir at 25° C. for 17 h Na2SO4 (20 g) was added stirring at 25° C. The resulting suspension was filtered through a pad of the Celite® reagent and Na2SO4 The filtrate was distilled to remove all solvents

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4,4,4-trifluoro-2-(2,2,2-trifluoroethyl)butan-1-ol (5.0 g, 24 mmol) in CH2Cl2 (80 mL) was added Dess-Martin periodinane reagent (10 g, 24 mmol). The reaction mixture was subsequently stirred for 20 hours at 25° C. The solution was diluted with Et2O (200 mL) and a 1:1 mixture of 10% sodium thiosulfate and saturated NaHCO3 (200 mL) was added. The mixture was stirred rapidly for 10 min until both phases were clear. The layers were separated and the aqueous phase was extracted with Et2O (100 mL). The combined organic layers were washed with brine (100 mL), dried over Na2SO4, filtered and concentrated to 50% of its original volume to give 4,4,4-trifluoro-2-(2,2,2-trifluoro-ethyl)-butyraldehyde that was used as is for the subsequent reaction. was added The mixture was stirred rapidly for 10 min until both phases The layers were separated the aqueous phase was extracted with Et2O (100 mL) The combined organic layers were washed with brine (100 mL) dried over Na2SO4 filtered concentrated to 50% of its original volume

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

Procedure: To a suspension of LAH (1.0 g) in Et2O (100 mL) at 25° C. was added slowly 4,4,4-trifluoro-2-(2,2,2-trifluoroethyl)-butyric acid ethyl ester (5.0 g, 19.8 mmol). The resulting mixture was stirred at reflux for 4 h. The cooled reaction mixture was quenched by sequential addition of water (1.0 mL), 15% NaOH in water (1.0 mL) and water (3.0 mL). After the resulting mixture was allowed to stir at 25° C. for 17 h, Na2SO4 (20 g) was added and stirring at 25° C. continued for 1 h. The resulting suspension was filtered through a pad of the Celite® reagent and Na2SO4. The filtrate was distilled to remove all solvents to afford the desired product as a colorless liquid (1.7 g, 41%). Mass Spectrum (−ESI): 269 [M+OAc]−. at reflux for 4 h The cooled reaction mixture was quenched by sequential addition of water (1.0 mL), 15% NaOH in water (1.0 mL) and water (3.0 mL) to stir at 25° C. for 17 h Na2SO4 (20 g) was added stirring at 25° C. The resulting suspension was filtered through a pad of the Celite® reagent and Na2SO4 The filtrate was distilled to remove all solvents

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 4,4,4-trifluoro-2-(2,2,2-trifluoroethyl)butan-1-ol (1.5 g, 7.14 mmol) in CH2Cl2 saturated with water (30 mL) was stirred under nitrogen at 0° C. Dess-Martin periodinane reagent (6.35 g, 14.99 mmol) was added in one portion. The resulting suspension was stirred at 25° C., monitoring the progress of reaction by TLC analysis (1:2 EtOAc/hexane). As the rate of conversion of the starting material slowed, additional 2 mL portions of CH2Cl2 saturated with water were added (three portions over 15 min). After 19 h at 25° C., the reaction was complete by TLC. The solution was diluted with Et2O (50 mL) and a solution of sodium thiosulfate, Na2S2O3 (73.33 mmol, 11.6 g, 11 eq) in 80% saturated aqueous sodium bicarbonate solution (50 mL) was added. The mixture was stirred rapidly for 10 min until both phases were clear. The layers were separated and the aqueous phase was extracted with ether (30 mL). The combined organic layers were washed sequentially with saturated aqueous sodium bicarbonate (10 mL) and brine (15 mL), then dried over MgSO4, filtered and concentrated to 50% of its original volume to give 4,4,4-trifluoro-2-(2,2,2-trifluoro-ethyl)-butyraldehyde as a solution (20 mL). Mass Spectrum (+ESI): (M+H)+. The mixture was stirred rapidly for 10 min until both phases The layers were separated the aqueous phase was extracted with ether (30 mL) The combined organic layers were washed sequentially with saturated aqueous sodium bicarbonate (10 mL) and brine (15 mL) dried over MgSO4 filtered concentrated to 50% of its original volume

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

Procedure: To a suspension of LAH (1.0 g) in Et2O (100 mL) at 25° C. was added slowly 4,4,4-trifluoro-2-(2,2,2-trifluoroethyl)-butyric acid ethyl ester (5.0 g, 19.8 mmol). The resulting mixture was stirred at reflux for 4 h. The cooled reaction mixture was quenched sequentially with water (1.0 mL), 15% NaOH in water (1.0 mL) and water (3.0 mL). After the resulting mixture was allowed to stir at 25° C. for 17 h, Na2SO4 (20 g) was added and stirring at 25° C. continued for 1 h. The resulting suspension was filtered through a pad of the Celite® reagent and Na2SO4. The filtrate was distilled to remove all solvents to afford the desired product as a colorless liquid (1.7 g, 41%). Mass Spectrum (−ESI): 269 [M+OAc]− at reflux for 4 h The cooled reaction mixture was quenched sequentially with water (1.0 mL), 15% NaOH in water (1.0 mL) and water (3.0 mL) to stir at 25° C. for 17 h Na2SO4 (20 g) was added stirring at 25° C. The resulting suspension was filtered through a pad of the Celite® reagent and Na2SO4 The filtrate was distilled to remove all solvents

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 4,4,4-trifluoro-2-(2,2,2-trifluoroethyl)butan-1-ol (1.5 g, 7.14 mmol) in CH2Cl2 saturated with water (30 mL) was stirred under nitrogen at 0° C. Dess-Martin periodinane reagent (6.35g, 14.99 mmol) was added in one portion. The resulting suspension was stirred at 25° C., monitoring the progress of reaction by TLC analysis (1:2 EtOAc/hexane). As the rate of conversion of the starting material slowed, additional 2 mL portions of CH2Cl2 saturated with water were added (three portions over 15 min). After 19 h at 25° C., the reaction was complete by TLC. The solution was diluted with Et2O (50 mL) and a solution of sodium thiosulfate, Na2S2O3 (73.33 mmol, 11.6g, 11 eq) in 80% saturated aqueous sodium bicarbonate solution (50 mL) was added. The mixture was stirred rapidly for 10 min until both phases were clear. The layers were separated and the aqueous phase was extracted with ether (30 mL). The combined organic layers were washed sequentially with saturated aqueous sodium bicarbonate (10 mL) and brine (15 mL), then dried over MgSO4, filtered and concentrated to 50% of its original volume to give 4,4,4-trifluoro-2-(2,2,2-trifluoro-ethyl)-butyraldehyde as a solution (20 mL). Mass Spectrum (+ESI): (M+H)+. The mixture was stirred rapidly for 10 min until both phases The layers were separated the aqueous phase was extracted with ether (30 mL) The combined organic layers were washed sequentially with saturated aqueous sodium bicarbonate (10 mL) and brine (15 mL) dried over MgSO4 filtered concentrated to 50% of its original volume

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

Procedure: To a suspension of LAH (1.0 g) in Et2O (100 mL) at 25° C. was added slowly 4,4,4-trifluoro-2-(2,2,2-trifluoroethyl)-butyric acid ethyl ester (5.0 g, 19.8 mmol). The resulting mixture was stirred at reflux for 4 h. The cooled reaction mixture was quenched sequentially with water (1.0 mL), 15% NaOH in water (1.0 mL) and water (3.0 mL). After the resulting mixture was allowed to stir at 25° C. for 17 h, Na2SO4 (20 g) was added and stirring at 25° C. continued for 1 h. The resulting suspension was filtered through a pad of the Celite® reagent and Na2SO4. The filtrate was distilled to remove all solvents to afford the desired product as a colorless liquid (1.7 g, 41%). Mass Spectrum (−ESI): 269 [M+OAc]− at reflux for 4 h The cooled reaction mixture was quenched sequentially with water (1.0 mL), 15% NaOH in water (1.0 mL) and water (3.0 mL) to stir at 25° C. for 17 h Na2SO4 (20 g) was added stirring at 25° C. The resulting suspension was filtered through a pad of the Celite® reagent and Na2SO4 The filtrate was distilled to remove all solvents