5,5,5-trifluoro-2-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoic acid

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

Procedure: To a stirred solution of 2-((tert-butoxycarbonyl)amino)-5,5,5-trifluoropentanoic acid (500 mg, 1.843 mmol) in THF (15 ml) cooled to −10° C. under a nitrogen atmosphere was added N-methylmorpholine (0.223 ml, 2.028 mmol) followed by isobutyl chloroformate (0.266 ml, 2.028 mmol) dropwise and stirred for 30 min. The reaction mixture was filtered. The filtrate was added to sodium borohydride (147 mg, 3.87 mmol) in water (10 mL) and stirred for 5 min. The mixture was diluted with ethyl acetate (10 mL). The organic layer was separated and washed with brine (2×10 mL), dried (Na2SO4) and evaporated under reduced pressure to afford tert-butyl (5,5,5-trifluoro-1-hydroxypentan-2-yl)carbamate (400 mg, 1.55 mmol, 84% yield) as a white solid which was taken to the next step without any purification. 1H NMR (400 MHz, CDCl3) δ 3.73-3.59 (m, 3H), 2.24-2.16 (m, 2H), 1.87-1.69 (m, 2H), 1.44 (s, 9H). The reaction mixture was filtered stirred for 5 min The organic layer was separated washed with brine (2×10 mL) dried (Na2SO4) evaporated under reduced pressure

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

Procedure: To a stirred solution of 2-amino-5,5,5-trifluoropentanoic acid hydrochloride (400 mg, 1.503 mmol) in THF (8 mL) and water (8 mL) was added K2CO3 (831 mg, 6.01 mmol) at rt and the solution was stirred for 10 min. To this mixture was added BOC2O (656 mg, 3.01 mmol). The reaction mixture was stirred for 8 h at rt. The reaction mixture was concentrated under reduced pressure. The aq. layer was washed with ethyl acetate (3×5 mL). The aqueous layer was acidified with saturated citric acid solution (5 mL) and then extracted with ethyl acetate (3×8 mL). The combined organic layers were washed with water (3×5 mL) followed by brine (10 mL), dried over sodium sulfate and concentrated under reduced pressure to afford 2-((tert-butoxycarbonyl)amino)-5,5,5-trifluoropentanoic acid (500 mg, 1.84 mmol) quantitatively as a colorless oil. The crude material was taken as such to the next step without further purification. 1H NMR (400 MHz, CDCl3) δ 5.04 (s, 1H), 4.38 (s, 1H), 2.15-2.28 (m, 2H), 1.91-1.95 (m, 2H), 1.46 (s, 9H). The reaction mixture was stirred for 8 h at rt The reaction mixture was concentrated under reduced pressure The aq. layer was washed with ethyl acetate (3×5 mL) extracted with ethyl acetate (3×8 mL) The combined organic layers were washed with water (3×5 mL) dried over sodium sulfate concentrated under reduced pressure

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

Procedure: To a stirred solution of 2-amino-5,5,5-trifluoropentanoic acid hydrochloride (400 mg, 1.503 mmol) in THF (8 mL) and water (8 mL) was added K2CO3 (831 mg, 6.01 mmol) at rt and the solution was stirred for 10 min. To this mixture was added BOC2O (656 mg, 3.01 mmol). The reaction mixture was stirred for 8 h at rt. The reaction mixture was concentrated under reduced pressure. The aq. layer was washed with ethyl acetate (3×5 mL). The aqueous layer was acidified with saturated citric acid solution (5 mL) and then extracted with ethyl acetate (3×8 mL). The combined organic layers were washed with water (3×5 mL) followed by brine (10 mL), dried over sodium sulfate and concentrated under reduced pressure to afford 2-((tert-butoxycarbonyl)amino)-5,5,5-trifluoropentanoic acid (500 mg, 1.84 mmol) quantitatively as a colorless oil. The crude material was taken as such to the next step without further purification. 1H NMR (400 MHz, CDCl3) δ 5.04 (s, 1H), 4.38 (s, 1H), 2.15-2.28 (m, 2H), 1.91-1.95 (m, 2H), 1.46 (s, 9H). The reaction mixture was stirred for 8 h at rt The reaction mixture was concentrated under reduced pressure The aq. layer was washed with ethyl acetate (3×5 mL) extracted with ethyl acetate (3×8 mL) The combined organic layers were washed with water (3×5 mL) dried over sodium sulfate concentrated under reduced pressure

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

Procedure: To a stirred solution of 2-((tert-butoxycarbonyl)amino)-5,5,5-trifluoropentanoic acid (500 mg, 1.843 mmol) in THF (15 ml) cooled to −10° C. under a nitrogen atmosphere was added N-methylmorpholine (0.223 ml, 2.028 mmol) followed by isobutyl chloroformate (0.266 ml, 2.028 mmol) dropwise and stirred for 30 min. The reaction mixture was filtered. The filtrate was added to sodium borohydride (147 mg, 3.87 mmol) in water (10 mL) and stirred for 5 min. The mixture was diluted with ethyl acetate (10 mL). The organic layer was separated and washed with brine (2×10 mL), dried (Na2SO4) and evaporated under reduced pressure to afford tert-butyl(5,5,5-trifluoro-1-hydroxypentan-2-yl)carbamate (400 mg, 1.55 mmol, 84% yield) as a white solid which was taken to the next step without any purification. 1H NMR (400 MHz, CDCl3) δ 3.73-3.59 (m, 3H), 2.24-2.16 (m, 2H), 1.87-1.69 (m, 2H), 1.44 (s, 9H). The reaction mixture was filtered stirred for 5 min The organic layer was separated washed with brine (2×10 mL) dried (Na2SO4) evaporated under reduced pressure

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

Procedure: To a stirred solution of 2-((tert-butoxycarbonyl)amino)-5,5,5-trifluoropentanoic acid (500 mg, 1.843 mmol) in THF (15 ml) cooled to −10° C. under a nitrogen atmosphere was added N-methylmorpholine (0.223 ml, 2.028 mmol) followed by isobutyl chloroformate (0.266 ml, 2.028 mmol) dropwise and stirred for 30 min. The reaction mixture was filtered. The filtrate was added to sodium borohydride (147 mg, 3.87 mmol) in water (10 mL) and stirred for 5 min. The mixture was diluted with ethyl acetate (10 mL). The organic layer was separated and washed with brine (2×10 mL), dried (Na2SO4) and evaporated under reduced pressure to afford tert-butyl(5,5,5-trifluoro-1-hydroxypentan-2-yl)carbamate (400 mg, 1.55 mmol, 84% yield) as a white solid which was taken to the next step without any purification. 1H NMR (400 MHz, CDCl3) δ 3.73-3.59 (m, 3H), 2.24-2.16 (m, 2H), 1.87-1.69 (m, 2H), 1.44 (s, 9H). The reaction mixture was filtered stirred for 5 min The organic layer was separated washed with brine (2×10 mL) dried (Na2SO4) evaporated under reduced pressure

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

Procedure: To a stirred solution of 2-((tert-butoxycarbonyl)amino)-5,5,5-trifluoropentanoic acid (500 mg, 1.843 mmol) in THF (15 ml) cooled to −10° C. under a nitrogen atmosphere was added N-methylmorpholine (0.223 ml, 2.028 mmol) followed by isobutyl chloroformate (0.266 ml, 2.028 mmol) dropwise and stirred for 30 min. The reaction mixture was filtered. The filtrate was added to sodium borohydride (147 mg, 3.87 mmol) in water (10 mL) and stirred for 5 min. The mixture was diluted with ethyl acetate (10 mL). The organic layer was separated and washed with brine (2×10 mL), dried (Na2SO4) and evaporated under reduced pressure to afford tert-butyl(5,5,5-trifluoro-1-hydroxypentan-2-yl)carbamate (400 mg, 1.55 mmol, 84% yield) as a white solid which was taken to the next step without any purification. 1H NMR (400 MHz, CDCl3) δ 3.73-3.59 (m, 3H), 2.24-2.16 (m, 2H), 1.87-1.69 (m, 2H), 1.44 (s, 9H). The reaction mixture was filtered stirred for 5 min The organic layer was separated washed with brine (2×10 mL) dried (Na2SO4) evaporated under reduced pressure

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

Procedure: To a stirred solution of 2-amino-5,5,5-trifluoropentanoic acid hydrochloride (400 mg, 1.503 mmol) in THF (8 mL) and water (8 mL) was added K2CO3 (831 mg, 6.01 mmol) at rt and the solution was stirred for 10 min. To this mixture was added BOC2O (656 mg, 3.01 mmol). The reaction mixture was stirred for 8 h at rt. The reaction mixture was concentrated under reduced pressure. The aq. layer was washed with ethyl acetate (3×5 mL). The aqueous layer was acidified with saturated citric acid solution (5 mL) and then extracted with ethyl acetate (3×8 mL). The combined organic layers were washed with water (3×5 mL) followed by brine (10 mL), dried over sodium sulfate and concentrated under reduced pressure to afford 2-((tert-butoxycarbonyl)amino)-5,5,5-trifluoropentanoic acid (500 mg, 1.84 mmol) quantitatively as a colorless oil. The crude material was taken as such to the next step without further purification. 1H NMR (400 MHz, CDCl3) δ 5.04 (s, 1H), 4.38 (s, 1H), 2.15-2.28 (m, 2H), 1.91-1.95 (m, 2H), 1.46 (s, 9H). The reaction mixture was stirred for 8 h at rt The reaction mixture was concentrated under reduced pressure The aq. layer was washed with ethyl acetate (3×5 mL) extracted with ethyl acetate (3×8 mL) The combined organic layers were washed with water (3×5 mL) dried over sodium sulfate concentrated under reduced pressure

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

Procedure: To a stirred solution of 2-((tert-butoxycarbonyl)amino)-5,5,5-trifluoropentanoic acid (500 mg, 1.843 mmol) in THF (15 mL) cooled to −10° C. under nitrogen atmosphere was added N-methylmorphline (0.223 mL, 2.028 mmol) followed by isobutyl chloroformate (0.266 mL, 2.028 mmol) dropwise. The solution was then stirred for 30 min then filtered. The filtrate was added to sodium borohydride (147 mg, 3.87 mmol) in water (10 mL), stirred for 5 min and diluted with ethyl acetate (10 mL). The organic layer was separated and washed with brine (2×10 mL), dried (Na2SO4) and evaporated under reduced pressure to afford tert-butyl (5,5,5-trifluoro-1-hydroxypentan-2-yl)carbamate (400 mg, 1.555 mmol, 84% yield) as a white solid which was taken to the next step without further purification. 1H NMR (400 MHz, MeOD) δ 3.44-3.56 (m, 3H), 2.16-2.26 (m, 2H), 1.83-1.92 (m, 1H), 1.57-1.67 (m, 1H), 1.47 (s, 9H). then filtered stirred for 5 min The organic layer was separated washed with brine (2×10 mL) dried (Na2SO4) evaporated under reduced pressure

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

Procedure: To a stirred solution of 2-((tert-butoxycarbonyl)amino)-5,5,5-trifluoropentanoic acid (500 mg, 1.843 mmol) in THF (15 ml) cooled to −10° C. under a nitrogen atmosphere was added N-methylmorpholine (0.223 ml, 2.028 mmol) followed by isobutyl chloroformate (0.266 ml, 2.028 mmol) dropwise and stirred for 30 min. The reaction mixture was filtered. The filtrate was added to sodium borohydride (147 mg, 3.87 mmol) in water (10 mL) and stirred for 5 min. The mixture was diluted with ethyl acetate (10 mL). The organic layer was separated and washed with brine (2×10 mL), dried (Na2SO4) and evaporated under reduced pressure to afford tert-butyl (5,5,5-trifluoro-1-hydroxypentan-2-yl)carbamate (400 mg, 1.55 mmol, 84% yield) as a white solid which was taken to the next step without any purification. 1H NMR (400 MHz, CDCl3) δ 3.73-3.59 (m, 3H), 2.24-2.16 (m, 2H), 1.87-1.69 (m, 2H), 1.44 (s, 9H). The reaction mixture was filtered stirred for 5 min The organic layer was separated washed with brine (2×10 mL) dried (Na2SO4) evaporated under reduced pressure

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

Procedure: To a stirred solution of 2-amino-5,5,5-trifluoropentanoic acid hydrochloride (400 mg, 1.503 mmol) in THF (8 mL) and water (8 mL) was added K2CO3 (831 mg, 6.01 mmol) at rt and the solution was stirred for 10 min. To this mixture was added BOC2O (656 mg, 3.01 mmol). The reaction mixture was stirred for 8 h at rt. The reaction mixture was concentrated under reduced pressure. The aq. layer was washed with ethyl acetate (3×5 mL). The aqueous layer was acidified with saturated citric acid solution (5 mL) and then extracted with ethyl acetate (3×8 mL). The combined organic layers were washed with water (3×5 mL) followed by brine (10 mL), dried over sodium sulfate and concentrated under reduced pressure to afford 2-((tert-butoxycarbonyl)amino)-5,5,5-trifluoropentanoic acid (500 mg, 1.84 mmol) quantitatively as a colorless oil. The crude material was taken as such to the next step without further purification. 1H NMR (400 MHz, CDCl3) δ 5.04 (s, 1H), 4.38 (s, 1H), 2.15-2.28 (m, 2H), 1.91-1.95 (m, 2H), 1.46 (s, 9H). The reaction mixture was stirred for 8 h at rt The reaction mixture was concentrated under reduced pressure The aq. layer was washed with ethyl acetate (3×5 mL) extracted with ethyl acetate (3×8 mL) The combined organic layers were washed with water (3×5 mL) dried over sodium sulfate concentrated under reduced pressure