4,4,4-trifluoro-3,3-dimethylbutanoic acid

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 4,4,4-trifluoro-3,3-dimethylbutanoic acid [See: US2010/0240663](0.6 g, 3.53 mmol) in thionyl chloride (6 mL, 82 mmol) was heated at 60° C. for 2 h, cooled to RT and concentrated to dryness. The residue was dissolved in DCM (2 mL), added drop-wise to a mixture of THF (8 mL) and NH4OH (˜15M, 8 mL, ˜120 mmol) and stirred at RT overnight. Solid NaCl was added until saturated, the mixture extracted with 4:1 DCM/THF (3×) and the combined organics were washed with satd. NaHCO3, then brine, dried over Na2SO4 and concentrated to dryness to afford 4,4,4-trifluoro-3,3-dimethylbutanamide (240 mg, 40%). 1H NMR (400 MHz, DMSO-d6): δ 7.46 (s, 1H), 6.93 (s, 1H), 2.20 (s, 2H), 1.18 (s, 6H). concentrated to dryness The residue was dissolved in DCM (2 mL) added drop-wise extracted with 4:1 DCM/THF (3×) the combined organics were washed with satd NaHCO3, then brine, dried over Na2SO4 concentrated to dryness

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 4,4,4-trifluoro-3,3-dimethylbutanoic acid [See: US2010/0240663](0.6 g, 3.53 mmol) in thionyl chloride (6 mL, 82 mmol) was heated at 60° C. for 2 h, cooled to RT and concentrated to dryness. The residue was dissolved in DCM (2 mL), added drop-wise to a mixture of THF (8 mL) and NH4OH (˜15M, 8 mL, ˜120 mmol) and stirred at RT overnight. Solid NaCl was added until saturated, the mixture extracted with 4:1 DCM/THF (3×) and the combined organics were washed with satd. NaHCO3, then brine, dried over Na2SO4 and concentrated to dryness to afford 4,4,4-trifluoro-3,3-dimethylbutanamide (240 mg, 40%). 1H NMR (400 MHz, DMSO-d6): δ 7.46 (s, 1H), 6.93 (s, 1H), 2.20 (s, 2H), 1.18 (s, 6H). concentrated to dryness The residue was dissolved in DCM (2 mL) added drop-wise extracted with 4:1 DCM/THF (3×) the combined organics were washed with satd NaHCO3, then brine, dried over Na2SO4 concentrated to dryness

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Treat a 0° C. solution of 4,4,4-trifluoro-3,3-dimethylbutanoic acid [See: US2010/0240663] (17 g, 100 mmol) in acetonitrile (200 mL) with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (23 g, 120 mmol) and 1-hydroxybenzotriazole (16.2 g, 120 mmol), stir at 0° C. for 2 h, treat with concentrated ammonia in water (25 wt %, 15 mL), allow to warm to RT and stir overnight. Remove the organics under reduced pressure, dissolve the residue in EtOAc, and wash with saturated. NaHCO3, then brine, dry over MgSO4, and concentrate to dryness. Treat the material with pet ether, collect the solid via filtration and dry to afford the title compound (13 g, 77% yield). 1H NMR (400 MHz, DMSO-d6): δ 7.46 (s, 1H), 6.93 (s, 1H), 2.19 (s, 2H), 1.18 (s, 6H). to warm to RT stir overnight Remove the organics under reduced pressure dissolve the residue in EtOAc wash with saturated NaHCO3, then brine, dry over MgSO4 concentrate to dryness Treat the material with pet ether collect the solid via filtration dry

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Treat a 0° C. solution of 4,4,4-trifluoro-3,3-dimethylbutanoic acid [See: US2010/0240663] (17 g, 100 mmol) in acetonitrile (200 mL) with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (23 g, 120 mmol) and 1-hydroxybenzotriazole (16.2 g, 120 mmol), stir at 0° C. for 2 h, treat with concentrated ammonia in water (25 wt %, 15 mL), allow to warm to RT and stir overnight. Remove the organics under reduced pressure, dissolve the residue in EtOAc, and wash with saturated. NaHCO3, then brine, dry over MgSO4, and concentrate to dryness. Treat the material with pet ether, collect the solid via filtration and dry to afford the title compound (13 g, 77% yield). 1H NMR (400 MHz, DMSO-d6): δ 7.46 (s, 1H), 6.93 (s, 1H), 2.19 (s, 2H), 1.18 (s, 6H). to warm to RT stir overnight Remove the organics under reduced pressure dissolve the residue in EtOAc wash with saturated NaHCO3, then brine, dry over MgSO4 concentrate to dryness Treat the material with pet ether collect the solid via filtration dry

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Treat a 0° C. solution of 4,4,4-trifluoro-3,3-dimethylbutanoic acid [See: US2010/0240663] (17 g, 100 mmol) in acetonitrile (200 mL) with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (23 g, 120 mmol) and 1-hydroxybenzotriazole (16.2 g, 120 mmol), stir at 0° C. for 2 h, treat with concentrated ammonia in water (25 wt %, 15 mL), allow to warm to RT and stir overnight. Remove the organics under reduced pressure, dissolve the residue in EtOAc, and wash with saturated. NaHCO3, then brine, dry over MgSO4, and concentrate to dryness. Treat the material with pet ether, collect the solid via filtration and dry to afford the title compound (13 g, 77% yield). 1H NMR (400 MHz, DMSO-d6): δ 7.46 (s, 1H), 6.93 (s, 1H), 2.19 (s, 2H), 1.18 (s, 6H). to warm to RT stir overnight Remove the organics under reduced pressure dissolve the residue in EtOAc wash with saturated NaHCO3, then brine, dry over MgSO4 concentrate to dryness Treat the material with pet ether collect the solid via filtration dry

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of diethyl 2-(1,1,1-trifluoro-2-methylpropan-2yl)malonate (iv, 20.93 g, 77.45 mmol) and KOH (17.23 g, 307.1 mmol) in EtOH (200 mL, 3000 mmol) was heated at 80° C. for 16 h. The reaction was concentrated and partitioned between water and Et2O. The aqueous layer was acidified with 6 N HCl and then extracted with Et2O (2×). The organic layers were combined, dried over MgSO4, filtered and concentrated to provide and orange oil. A low pressure distillation gave the product as a light pink liquid (10.17 g, 77%). The reaction was concentrated partitioned between water and Et2O extracted with Et2O (2×) dried over MgSO4 filtered concentrated to provide A low pressure distillation

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of diethyl 2-(1,1,1-trifluoro-2-methylpropan-2-yl)malonate (iv, 20.93 g, 77.45 mmol) and KOH (17.23 g, 307.1 mmol) in EtOH (200 mL, 3000 mmol) was heated at 80° C. for 16 h. The reaction was concentrated and partitioned between water and Et2O. The aqueous layer was acidified with 6 N HCl and then extracted with Et2O (2×). The organic layers were combined, dried over MgSO4, filtered and concentrated to provide and orange oil. A low pressure distillation gave the product as a light pink liquid (10.17 g, 77%). The reaction was concentrated partitioned between water and Et2O extracted with Et2O (2×) dried over MgSO4 filtered concentrated to provide A low pressure distillation

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 4,4,4-trifluoro-3,3-dimethylbutanoic acid [See: US2010/0240663](0.6 g, 3.53 mmol) in thionyl chloride (6 mL, 82 mmol) was heated at 60° C. for 2 h, cooled to RT and concentrated to dryness. The residue was dissolved in DCM (2 mL), added drop-wise to a mixture of THF (8 mL) and NH4OH (˜15M, 8 mL, ˜120 mmol) and stirred at RT overnight. Solid NaCl was added until saturated, the mixture extracted with 4:1 DCM/THF (3×) and the combined organics were washed with satd. NaHCO3, then brine, dried over Na2SO4 and concentrated to dryness to afford 4,4,4-trifluoro-3,3-dimethylbutanamide (240 mg, 40%). 1H NMR (400 MHz, DMSO-d6): δ 7.46 (s, 1H), 6.93 (s, 1H), 2.20 (s, 2H), 1.18 (s, 6H). concentrated to dryness The residue was dissolved in DCM (2 mL) added drop-wise extracted with 4:1 DCM/THF (3×) the combined organics were washed with satd NaHCO3, then brine, dried over Na2SO4 concentrated to dryness

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Treat a 0° C. solution of 4,4,4-trifluoro-3,3-dimethylbutanoic acid [See: US2010/0240663] (17 g, 100 mmol) in acetonitrile (200 mL) with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (23 g, 120 mmol) and 1-hydroxybenzotriazole (16.2 g, 120 mmol), stir at 0° C. for 2 h, treat with concentrated ammonia in water (25 wt %, 15 mL), allow to warm to RT and stir overnight. Remove the organics under reduced pressure, dissolve the residue in EtOAc, and wash with saturated. NaHCO3, then brine, dry over MgSO4, and concentrate to dryness. Treat the material with pet ether, collect the solid via filtration and dry to afford the title compound (13 g, 77% yield). 1H NMR (400 MHz, DMSO-d6): δ 7.46 (s, 1H), 6.93 (s, 1H), 2.19 (s, 2H), 1.18 (s, 6H). to warm to RT stir overnight Remove the organics under reduced pressure dissolve the residue in EtOAc wash with saturated NaHCO3, then brine, dry over MgSO4 concentrate to dryness Treat the material with pet ether collect the solid via filtration dry

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Treat a 0° C. solution of 4,4,4-trifluoro-3,3-dimethylbutanoic acid [See: US2010/0240663] (17 g, 100 mmol) in acetonitrile (200 mL) with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (23 g, 120 mmol) and 1-hydroxybenzotriazole (16.2 g, 120 mmol), stir at 0° C. for 2 h, treat with concentrated ammonia in water (25 wt %, 15 mL), allow to warm to RT and stir overnight. Remove the organics under reduced pressure, dissolve the residue in EtOAc, and wash with saturated. NaHCO3, then brine, dry over MgSO4, and concentrate to dryness. Treat the material with pet ether, collect the solid via filtration and dry to afford the title compound (13 g, 77% yield). 1H NMR (400 MHz, DMSO-d6): δ 7.46 (s, 1H), 6.93 (s, 1H), 2.19 (s, 2H), 1.18 (s, 6H). to warm to RT stir overnight Remove the organics under reduced pressure dissolve the residue in EtOAc wash with saturated NaHCO3, then brine, dry over MgSO4 concentrate to dryness Treat the material with pet ether collect the solid via filtration dry