2,2,2-trifluoroethyl 2,2,2-trifluoroacetate

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

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

Procedure: To a suspension of 60% NaH (2.2 g, 55 mmol; washed with hexanes) in THF (250 mL) at 0° C. was added dropwise tert-butyl acetoacetate (8.0 g, 50.6 mmol) over a period of 15 min. The mixture was stirred for 15 min. and a homogenous solution solution resulted. A solution of 2.5M n-BuLi in hexanes (20.5 mL, 51 mmol) was added dropwise. After stirring for 15 min., 2,2,2-trifluoroethyl trifluoroacetate (11 g, 56 mmol) was added and the mixture was stirred for 30 min., quenched with HOAc, diluted with H2O and extracted with EtOAc. The EtOAc extract was washed with H2O, dried (anhydrous MgSO4) and concentrated. Chromatography over silica gel and elution with hexanes:EtOAc (10:1), then hexanes:EtOAc (4:1) provided 5 g of title compound as a red-brown oil. a homogenous solution solution resulted After stirring for 15 min. the mixture was stirred for 30 min. quenched with HOAc diluted with H2O extracted with EtOAc The EtOAc extract was washed with H2O dried (anhydrous MgSO4) concentrated Chromatography over silica gel and elution with hexanes:EtOAc (10:1)

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

Procedure: After five cycles similar to the one described above, the gas chromatographic analysis showed only 80% conversion to trifluoroethanol and the catalyst was then regenerated in the following manner. The pressure tube containing the catalyst residue (originally 0.03 mmol) was charged with 20 mg (0.25 mmol) of NaBH(OCH3)3, in a dry box. Tetrahydrofuran (3 ml) was distilled into the tube under vacuum and the solution stirred at room temperature for one hour. The solvent and other volatiles were removed in vacuo and the residue evacuated to dryness. The pressure tube was then charged with toluene (3 ml) and 1.1 gram (5.7 mmols) of ester and the hydrogenation was conducted as described in part (a). The pressure tube containing the catalyst residue (originally 0.03 mmol) Tetrahydrofuran (3 ml) was distilled into the tube under vacuum The solvent and other volatiles were removed in vacuo the residue evacuated to dryness

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

Procedure: After five cycles similar to the one described above, the gas chromatographic analysis showed only 80% conversion to trifluoroethanol and the catalyst was then regenerated in the following manner. The pressure tube containing the catalyst residue (originally 0.03 mmol) was charged with 20 mg (0.25 mmol) of NaBH(OCH3)3, in a dry box. Tetrahydrofuran (3 ml) was distilled into the tube under vacuum and the solution stirred at room temperature for one hour. The solvent and other volatiles were removed in vacuo and the residue evacuated to dryness. The pressure tube was then charged with toluene (3 ml) and 1.1 gram (5.7 mmols) of ester and the hydrogenation was conducted as described in part (a). The pressure tube containing the catalyst residue (originally 0.03 mmol) Tetrahydrofuran (3 ml) was distilled into the tube under vacuum The solvent and other volatiles were removed in vacuo the residue evacuated to dryness

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

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

Procedure: To a 0° C. solution of LiHMDS (0.65 mL, 0.6 M in THF) was added a solution of 1-indanone (26 mg, 0.19 mmol) in THF (1.0 mL). The reaction mixture was allowed to warm to room temperature over 20 min, and then CF3CO2CH2CF3 was added (55 μL, 0.41 mmol). After an additional 20 min at room temperature, saturated aqueous NH4Cl (5 mL) was added, and the resulting mixture was extracted with EtOAc (3×5 mL). The organics were dried over Na2SO4 and concentrated under reduced pressure. Without purification, the crude mixture was immediately subjected to general procedure B. SiO2 flash chromatography (25% EtOAc in hexanes) afforded the 2-methlyene-1-indanone as a yellow oil (28 mg) in 98% yield. the resulting mixture was extracted with EtOAc (3×5 mL) The organics were dried over Na2SO4 concentrated under reduced pressure Without purification

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

Procedure: A 250 ml three-neck flask fitted with KPG stirrer, dry-ice condenser and dropping funnel was charged with 23.11 g (0.2 mole) of pyridinium hydrochloride and 20.0 g (0.2 mole) of 2,2,2-trifluoroethanol. Subsequently, at an internal reaction temperature from 52° to 55° C., 42.01 g (0.2 mole) of trifluoroacetic anhydride were added dropwise over a period 3 hours. The yield of trifluoroethyl trifluoroacetate was 98% (GC). The resulting reaction solution was either used as catalyst mixture for experiments as described in Example 1, or 2,2,2-trifluoroethanol was distilled off. During the course of the distillation the trifluoroacetic acid, which initially formed in the reaction, reacted in the distillation flask with the pyridinium hydrochloride to form pyridinium trifluoroacetate and HCl. The resulting reaction solution was distilled off During the course of the distillation the trifluoroacetic acid, which initially formed in the reaction

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

Procedure: 30 g (0.16 mole) of pyridinium trifluoroacetate in 355 g (3.55 mole) of 2,2,2-trifluoroethanol were introduced as an initial charge into a laboratory circulating reactor apparatus (one-liter four-necked flask fitted with KPG stirrer, a Prominent pump, and a 30 cm column packed with Raschig rings), and the initial charge was circulated at an internal temperature of 54° C. 134 g (1.01 mole) of trifluoroacetyl chloride were subsequently metered into the flask via an immersed inlet tube over a period of 100 minutes. After the trifluoroacetyl chloride addition was complete, the mixture was allowed to react for a further 10 minutes. Subsequent fractional distillation of the reaction mixture via a Vigreux column (temperature at the distillation head: from 54° to 56° C.) yielded 177.8 g of trifluoroethyl trifluoroacetate, corresponding to 89.8% of the theoretical yield. The trifluoroethanol/pyridinium salt mixture remaining in the reservoir flask can be used again for esterification with equal effectiveness. an initial charge into a laboratory fitted with KPG stirrer initial charge was circulated at an internal temperature of 54° C to react for a further 10 minutes Subsequent fractional distillation of the reaction mixture via a Vigreux column (temperature at the distillation head

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

Procedure: To a suspension of 60% NaH (2.2 g, 55 mmol; washed with hexanes) in THF (250 mL) at 0° C. was added dropwise tert-butyl acetoacetate (8.0 g, 50.6 mmol) over a period of 15 min. The mixture was stirred for 15 min. and a homogenous solution solution resulted. A solution of 2.5M n-BuLi in hexanes (20.5 mL, 51 mmol) was added dropwise. After stirring for 15 min., 2,2,2-trifluoroethyl trifluoroacetate (11 g, 56 mmol) was added and the mixture was stirred for 30 min., quenched with HOAc, diluted with H2O and extracted with EtOAc. The EtOAc extract was washed with H2O, dried (anhydrous MgSO4) and concentrated. Chromatography over silica gel and elution with hexanes:EtOAc (10:1), then hexanes:EtOAc (4:1) provided 5 g of title compound as a red-brown oil. a homogenous solution solution resulted After stirring for 15 min. the mixture was stirred for 30 min. quenched with HOAc diluted with H2O extracted with EtOAc The EtOAc extract was washed with H2O dried (anhydrous MgSO4) concentrated Chromatography over silica gel and elution with hexanes:EtOAc (10:1)

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

Procedure: After five cycles similar to the one described above, the gas chromatographic analysis showed only 80% conversion to trifluoroethanol and the catalyst was then regenerated in the following manner. The pressure tube containing the catalyst residue (originally 0.03 mmol) was charged with 20 mg (0.25 mmol) of NaBH(OCH3)3, in a dry box. Tetrahydrofuran (3 ml) was distilled into the tube under vacuum and the solution stirred at room temperature for one hour. The solvent and other volatiles were removed in vacuo and the residue evacuated to dryness. The pressure tube was then charged with toluene (3 ml) and 1.1 gram (5.7 mmols) of ester and the hydrogenation was conducted as described in part (a). The pressure tube containing the catalyst residue (originally 0.03 mmol) Tetrahydrofuran (3 ml) was distilled into the tube under vacuum The solvent and other volatiles were removed in vacuo the residue evacuated to dryness