4-fluoro-3,3-dimethyl-2-oxobutanoic acid

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

実験手順: To a solution of 4-fluoro-3,3-dimethyl-2-oxobutanoic acid (2.3 g, 15.53 mmol) in DMF (30 mL) was added iodoethane (1.880 mL, 23.29 mmol) and K2CO3 (5.36 g, 38.8 mmol). The reaction mixture was stirred at rt for 18 h. The reaction mixture was diluted with EtOAc and stirred for 10 min. The solid was filtered. The filtration was partitioned between EtOAc and water. The organic phase was washed water, sat. NaCl, and concentrated. The residue was diluted with hexane (˜100 mL) and washed with water (2×30 mL), dried over MgSO4, filtered and concentrated to yield ethyl 4-fluoro-3,3-dimethyl-2-oxobutanoate (2.3 g). stirred for 10 min The solid was filtered The filtration was partitioned between EtOAc and water The organic phase was washed water, sat. NaCl concentrated The residue was diluted with hexane (˜100 mL) washed with water (2×30 mL) dried over MgSO4 filtered concentrated

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

実験手順: To a vigorous stirring mixture of 4-fluoro-3,3-dimethylbutan-2-one (4.1 g, 34.7 mmol) in water (50 mL) and NaOH (7 mL, 70.0 mmol) cooled in an ice-acetone bath was added portionwise potassium permanganate (9.87 g, 62.5 mmol). The inner temperature was controlled between −3 to 2° C. during the addition process. Upon the completion of the addition, the reaction mixture was stirred in the ice-acetone bath for 6 hrs and then allowed to warm up. EtOH (5 mL) was added and the reaction mixture was stirred for another 15 min. The reaction mixture was filtered and the solid was washed with water (˜80 mL). The filtration was acidified with 6 N HCl, and extracted with EtOAc. The combined extracts were washed with 1N HCl, sat. NaCl, dried (Na2SO4), filtered and concentrated to yield 4-fluoro-3,3-dimethyl-2-oxobutanoic acid (2.3 g). cooled in an ice-acetone bath was controlled between −3 to 2° C. during the addition process Upon the completion of the addition to warm up The reaction mixture was filtered the solid was washed with water (˜80 mL) The filtration extracted with EtOAc The combined extracts were washed with 1N HCl, sat. NaCl dried (Na2SO4) filtered concentrated

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

実験手順: To a solution of 4-fluoro-3,3-dimethyl-2-oxobutanoic acid (2.3 g, 15.53 mmol) in DMF (30 mL) was added iodoethane (1.880 mL, 23.29 mmol) and K2CO3 (5.36 g, 38.8 mmol). The reaction mixture was stirred at rt for 18 h. The reaction mixture was diluted with EtOAc and stirred for 10 min. The solid was filtered. The filtration was partitioned between EtOAc and water. The organic phase was washed water, sat. NaCl, and concentrated. The residue was diluted with hexane (˜100 mL) and washed with water (2×30 mL), dried over MgSO4, filtered and concentrated to yield ethyl 4-fluoro-3,3-dimethyl-2-oxobutanoate (2.3 g). stirred for 10 min The solid was filtered The filtration was partitioned between EtOAc and water The organic phase was washed water, sat. NaCl concentrated The residue was diluted with hexane (˜100 mL) washed with water (2×30 mL) dried over MgSO4 filtered concentrated

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

実験手順: To a vigorous stirring mixture of 4-fluoro-3,3-dimethylbutan-2-one (4.1 g, 34.7 mmol) in water (50 mL) and NaOH (7 mL, 70.0 mmol) cooled in an ice-acetone bath was added portionwise potassium permanganate (9.87 g, 62.5 mmol). The inner temperature was controlled between −3 to 2° C. during the addition process. Upon the completion of the addition, the reaction mixture was stirred in the ice-acetone bath for 6 hrs and then allowed to warm up. EtOH (5 mL) was added and the reaction mixture was stirred for another 15 min. The reaction mixture was filtered and the solid was washed with water (˜80 mL). The filtration was acidified with 6 N HCl, and extracted with EtOAc. The combined extracts were washed with 1N HCl, sat. NaCl, dried (Na2SO4), filtered and concentrated to yield 4-fluoro-3,3-dimethyl-2-oxobutanoic acid (2.3 g). cooled in an ice-acetone bath was controlled between −3 to 2° C. during the addition process Upon the completion of the addition to warm up The reaction mixture was filtered the solid was washed with water (˜80 mL) The filtration extracted with EtOAc The combined extracts were washed with 1N HCl, sat. NaCl dried (Na2SO4) filtered concentrated