N-tert-butyl-4-chlorobenzamide

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:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of N-tert-butyl4-chlorobenzamide (1.06 g, 5.00 mmol) in anhydrous THF (20 mL) was cooled to −78° C. under nitrogen. To the stirred solution was added dropwise tert-butyllithium solution in pentane (1.7M, 7.3 mL, 12.5 mmol), such that the internal temperature remained below −70° C. The resulting suspension gradually turned from pale to bright yellow. The mixture was stirred for an additional 1 hour at −78° C. DMF (1.5 mL, 19.5 mmol) was added dropwise to the slurry below −70° C. resulting in formation of a clear light yellow solution. The solution was allowed to warm to −20° C. (became colorless) before it was quenched with sat. aq. NH4Cl (10 mL) and allowed to warm to RT. The biphasic mixture was diluted with ethyl acetate (20 mL), and the layers were seperated. The organic layer was washed with water (20 mL), brine (20 mL), and dried over anhydrous MgSO4. The organic solvent was removal under reduced pressure to afford 2-tert-butyl-5-chloro-3-hydroxyisoindolin-1-one (1.18 g, 98% yield) as a colorless solid. remained below −70° C resulting in formation of a clear light yellow solution to warm to −20° C. (became colorless) before it was quenched with sat. aq. NH4Cl (10 mL) to warm to RT The biphasic mixture was diluted with ethyl acetate (20 mL) the layers were seperated The organic layer was washed with water (20 mL), brine (20 mL) dried over anhydrous MgSO4 removal under reduced pressure

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of N-tert-butyl4-chlorobenzamide (1.06 g, 5.00 mmol) in anhydrous THF (20 mL) was cooled to −78° C. under nitrogen. To the stirred solution was added dropwise tert-butyllithium solution in pentane (1.7M, 7.3 mL, 12.5 mmol), such that the internal temperature remained below −70° C. The resulting suspension gradually turned from pale to bright yellow. The mixture was stirred for an additional 1 hour at −78° C. DMF (1.5 mL, 19.5 mmol) was added dropwise to the slurry below −70° C. resulting in formation of a clear light yellow solution. The solution was allowed to warm to −20° C. (became colorless) before it was quenched with sat. aq. NH4Cl (10 mL) and allowed to warm to RT. The biphasic mixture was diluted with ethyl acetate (20 mL), and the layers were seperated. The organic layer was washed with water (20 mL), brine (20 mL), and dried over anhydrous MgSO4. The organic solvent was removal under reduced pressure to afford 2-tert-butyl-5-chloro-3-hydroxyisoindolin-1-one (1.18 g, 98% yield) as a colorless solid. remained below −70° C resulting in formation of a clear light yellow solution to warm to −20° C. (became colorless) before it was quenched with sat. aq. NH4Cl (10 mL) to warm to RT The biphasic mixture was diluted with ethyl acetate (20 mL) the layers were seperated The organic layer was washed with water (20 mL), brine (20 mL) dried over anhydrous MgSO4 removal under reduced pressure

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of N-tert-butyl4-chlorobenzamide (1.06 g, 5.00 mmol) in anhydrous THF (20 mL) was cooled to −78° C. under nitrogen. To the stirred solution was added dropwise tert-butyllithium solution in pentane (1.7M, 7.3 mL, 12.5 mmol), such that the internal temperature remained below −70° C. The resulting suspension gradually turned from pale to bright yellow. The mixture was stirred for an additional 1 hour at −78° C. DMF (1.5 mL, 19.5 mmol) was added dropwise to the slurry below −70° C. resulting in formation of a clear light yellow solution. The solution was allowed to warm to −20° C. (became colorless) before it was quenched with sat. aq. NH4Cl (10 mL) and allowed to warm to RT. The biphasic mixture was diluted with ethyl acetate (20 mL), and the layers were seperated. The organic layer was washed with water (20 mL), brine (20 mL), and dried over anhydrous MgSO4. The organic solvent was removal under reduced pressure to afford 2-tert-butyl-5-chloro-3-hydroxyisoindolin-1-one (1.18 g, 98% yield) as a colorless solid. remained below −70° C resulting in formation of a clear light yellow solution to warm to −20° C. (became colorless) before it was quenched with sat. aq. NH4Cl (10 mL) to warm to RT The biphasic mixture was diluted with ethyl acetate (20 mL) the layers were seperated The organic layer was washed with water (20 mL), brine (20 mL) dried over anhydrous MgSO4 removal under reduced pressure

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

実験手順: To a stirred suspension of 4-chlorobenzoic acid (31.3 g, 200 mmol) in toluene (200 mL) was added oxalyl chloride (30 mL, 350 mmol) followed by DMF (0.1 mL). The resulting suspension was heated at reflux until all solids dissolved. The solvent was removed under reduced pressure by rotary evaporation. The resulting semi-solid residue was dissolved in ethyl acetate (200 mL) and cooled in an ice bath under nitrogen with mechanical stirring. A solution of tert-butylamine (53 mL, 500 mmol) in ethyl acetate (50 mL) was carefully added to the mixture dropwise keeping the internal temperature below 10° C. During addition the initially clear solution became thick colorless slurry. Ethyl acetate (50 mL) was added followed by sat. aq. NaHCO3 (300 mL) and the resulting mixture was stirred until two clear layers resulted. The biphasic mixture was transferred into a separatory funnel, and the organic layer was separated. The organic layer was then washed with water (100 mL), brine (100 mL), and dried over anhydrous Na2SO4. Recrystallization from ethyl acetate/hexanes afforded N-tert-butyl-4-chlorobenzamide (35.5 g, 84% yield) as colorless needles (mp 136-137° C.). The resulting suspension was heated at reflux until all solids dissolved The solvent was removed under reduced pressure by rotary evaporation The resulting semi-solid residue was dissolved in ethyl acetate (200 mL) cooled in an ice bath under nitrogen with mechanical stirring the internal temperature below 10° C During addition the initially clear solution resulted The biphasic mixture was transferred into a separatory funnel the organic layer was separated The organic layer was then washed with water (100 mL), brine (100 mL) dried over anhydrous Na2SO4 Recrystallization from ethyl acetate/hexanes