ethyl 4,4,4-trifluoro-2-methylbutanoate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: A solution of diisopropylamine (19.5 mL) in tetrahydrofuran (200 mL) at 0° C. was treated with n-butyllithium (71 mL, 1.5M in hexanes). The resulting solution was stirred for 30 minutes at 0° C., then was cooled to -70° C. A solution of ethyl 4,4,4-trifluorobutyrate (14 mL) in tetrahydrofuran (150 mL) was slowly added to the lithium diisopropylamide solution and the resulting mixture was stirred at -70° C. for 30 minutes. A solution of iodomethane (11.5 mL) in tetrahydrofuran was added in one portion, the cooling bath was removed, and the reaction mixture was allowed to warm to room temperature. The reaction mixture was quenched with water and evaporated. The residue was dissolved in methylene chloride, washed (10% (w/v) hydrochloric acid, water, and brine), dried (MgSO4), filtered, and evaporated. The resulting pale yellow liquid was purified by distillation to yield ethyl 4,4,4-trifluoro-2-methylbutyrate as a colorless liquid (7.8 g, 46%); bp 125°-128 ° C.; partial NMR: (300 MHz, CDCl3): 1.30 (m, 6H, CH3), CH2CH3), 2.15 (m, 1H, H-C(3)), 2.64 (m, 1H, H-C(3)), 2.72 (m, 1H, H-C(2)), 4.16 (q, 2H, OCH2). was cooled to -70° C the resulting mixture was stirred at -70° C. for 30 minutes the cooling bath was removed to warm to room temperature The reaction mixture was quenched with water evaporated The residue was dissolved in methylene chloride washed (10% (w/v) hydrochloric acid, water, and brine) dried (MgSO4) filtered evaporated The resulting pale yellow liquid was purified by distillation

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

実験手順: A solution of diisopropylamine (19.5 mL) in tetrahydrofuran (200 mL) at 0° C. was treated with n-butyllithium (71 mL, 1.5M in hexanes). The resulting solution was stirred for 30 minutes at 0° C., then was cooled to -70° C. A solution of ethyl 4,4,4-trifluorobutyrate (14 mL) in tetrahydrofuran (150 mL) was slowly added to the lithium diisopropylamide solution and the resulting mixture was stirred at -70° C. for 30 minutes. A solution of iodomethane (11.5 mL) in tetrahydrofuran was added in one portion, the cooling bath was removed, and the reaction mixture was allowed to warm to room temperature. The reaction mixture was quenched with water and evaporated. The residue was dissolved in methylene chloride, washed (10% (w/v) hydrochloric acid, water, and brine), dried (MgSO4), filtered, and evaporated. The resulting pale yellow liquid was purified by distillation to yield ethyl 4,4,4-trifluoro-2-methylbutyrate as a colorless liquid (7.8 g, 46%); bp 125°-128 ° C.; partial NMR: (300 MHz, CDCl3): 1.30 (m, 6H, CH3), CH2CH3), 2.15 (m, 1H, H-C(3)), 2.64 (m, 1H, H-C(3)), 2.72 (m, 1H, H-C(2)), 4.16 (q, 2H, OCH2). was cooled to -70° C the resulting mixture was stirred at -70° C. for 30 minutes the cooling bath was removed to warm to room temperature The reaction mixture was quenched with water evaporated The residue was dissolved in methylene chloride washed (10% (w/v) hydrochloric acid, water, and brine) dried (MgSO4) filtered evaporated The resulting pale yellow liquid was purified by distillation

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

実験手順: A solution of ethyl 4,4,4-trifluoro-2-methylbutyrate (7.7 g) in methanol (21 mL), tetrahydrofuran (21 mL) and water (8.4 mL) was treated with lithium hydroxide monohydrate (3.5 g). The mixture was stirred for 48 hours and the organic solvents evaporated. The resulting aqueous solution was diluted with water and acidified with 6N hydrochloric acid. The aqueous solution was exhaustively extracted with ethyl acetate. The combined organic extract was washed (water and brine), dried (MgSO4), filtered and evaporated to give 4,4,4-trifluoro-2-methylbutyric acid as a pale yellow liquid (6.5 g, 99%); partial NMR (300 MHz, CDCl3): 1.34 (d, 3H, CH3), 2.18 (m, 1H, H-C(3)), 2.67, (m, 1H, H-C(3)), 2.74 (m, 1H, H-C(2)), 10.6 (br, 1H, CO2H). the organic solvents evaporated The resulting aqueous solution was diluted with water The aqueous solution was exhaustively extracted with ethyl acetate The combined organic extract was washed (water and brine) dried (MgSO4) filtered evaporated

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

実験手順: A solution of ethyl 4,4,4-trifluoro-2-methylbutyrate (7.7 g) in methanol (21 mL), tetrahydrofuran (21 mL) and water (8.4 mL) was treated with lithium hydroxide monohydrate (3.5 g). The mixture was stirred for 48 hours and the organic solvents evaporated. The resulting aqueous solution was diluted with water and acidified with 6N hydrochloric acid. The aqueous solution was exhaustively extracted with ethyl acetate. The combined organic extract was washed (water and brine), dried (MgSO4), filtered and evaporated to give 4,4,4-trifluoro-2-methylbutyric acid as a pale yellow liquid (6.5 g, 99%); partial NMR (300 MHz, CDCl3): 1.34 (d, 3H, CH3), 2.18 (m, 1H, H-C(3)), 2.67, (m, 1H, H-C(3)), 2.74 (m, 1H, H-C(2)), 10.6 (br, 1H, CO2H). the organic solvents evaporated The resulting aqueous solution was diluted with water The aqueous solution was exhaustively extracted with ethyl acetate The combined organic extract was washed (water and brine) dried (MgSO4) filtered evaporated

反応条件: temp:0.00; pressure:0.00; stir: