ethyl 4-fluoro-3,3-dimethyl-2-oxobutanoate

反応条件: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of ethyl 4-fluoro-3,3-dimethyl-2-oxobutanoate (2.3 g, 13.05 mmol) in THF (20 mL) was added (S)-2-methylpropane-2-sulfinamide (1.899 g, 15.67 mmol) and tetraethoxytitanium (5.91 mL, 26.1 mmol). The reaction mixture was heated at 65° C. for 6 h. The reaction mixture was cooled down, diluted with EtOAc and sat. NaCl (40 mL) and stirred at rt for 0.5 h. The solid was filtered and washed with water and EtOAc. The filtrate was separated and the organic layer was washed with water, sat. NaCl, dried (MgSO4) and purified by flash chromatography (EtOAc/hexane) to afford (S)-ethyl 2-(tert-butylsulfinylimino)-4-fluoro-3,3-dimethylbutanoate (1.1 g). 1H NMR (400 MHz, CDCl3) δ ppm 4.46-4.53 (1H, m), 4.28-4.42 (3H, m), 1.59 (3H, s), 1.21-1.31 (15H, m). The reaction mixture was cooled down The solid was filtered washed with water and EtOAc The filtrate was separated the organic layer was washed with water, sat. NaCl dried (MgSO4) purified by flash chromatography (EtOAc/hexane)

反応条件: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of ethyl 4-fluoro-3,3-dimethyl-2-oxobutanoate (2.3 g, 13.05 mmol) in THF (20 mL) was added (S)-2-methylpropane-2-sulfinamide (1.899 g, 15.67 mmol) and tetraethoxytitanium (5.91 mL, 26.1 mmol). The reaction mixture was heated at 65° C. for 6 h. The reaction mixture was cooled down, diluted with EtOAc and sat. NaCl (40 mL) and stirred at rt for 0.5 h. The solid was filtered and washed with water and EtOAc. The filtrate was separated and the organic layer was washed with water, sat. NaCl, dried (MgSO4) and purified by flash chromatography (EtOAc/hexane) to afford (S)-ethyl 2-(tert-butylsulfinylimino)-4-fluoro-3,3-dimethylbutanoate (1.1 g). 1H NMR (400 MHz, CDCl3) δ ppm 4.46-4.53 (1H, m), 4.28-4.42 (3H, m), 1.59 (3H, s), 1.21-1.31 (15H, m). The reaction mixture was cooled down The solid was filtered washed with water and EtOAc The filtrate was separated the organic layer was washed with water, sat. NaCl dried (MgSO4) purified by flash chromatography (EtOAc/hexane)

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:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of ethyl 4-fluoro-3,3-dimethyl-2-oxobutanoate (2.3 g, 13.05 mmol) in THF (20 mL) was added (S)-2-methylpropane-2-sulfinamide (1.899 g, 15.67 mmol) and tetraethoxytitanium (5.91 mL, 26.1 mmol). The reaction mixture was heated at 65° C. for 6 h. The reaction mixture was cooled down, diluted with EtOAc and sat. NaCl (40 mL) and stirred at rt for 0.5 h. The solid was filtered and washed with water and EtOAc. The filtrate was separated and the organic layer was washed with water, sat. NaCl, dried (MgSO4) and purified by flash chromatography (EtOAc/hexane) to afford (S)-ethyl 2-(tert-butylsulfinylimino)-4-fluoro-3,3-dimethylbutanoate (1.1 g). 1H NMR (400 MHz, CDCl3) δ ppm 4.46-4.53 (1H, m), 4.28-4.42 (3H, m), 1.59 (3H, s), 1.21-1.31 (15H, m). The reaction mixture was cooled down The solid was filtered washed with water and EtOAc The filtrate was separated the organic layer was washed with water, sat. NaCl dried (MgSO4) purified by flash chromatography (EtOAc/hexane)

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