Dimethylformamide → 2-Tert-butyl-5-chloro-3-hydroxyisoindolin-1-one

Participants

Reaction Conditions

Reaction Steps

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.

Provenance & Evidence