Methyl iodide → 2-[(1R,2S)-5-chloro-2-methoxy-2,3-dihydro-1H-inden-1-yl]-1H-isoindole-1,3(2H)-dione

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-[(1R,2S)-5-chloro-2-hydroxy-2,3-dihydro-1H-inden-1-yl]-1H-isoindole-1,3(2H)-dione (25.8 g, 0.0822 mol) in tetrahydrofuran (186 mL, 2.29 mol) was added methyl iodide (20.5 mL, 0.329 mol) and the solution was stirred at 0° C. To this solution was added 1.00 M of potassium tert-butoxide in tetrahydrofuran (90.4 mL, 0.0904 mol) dropwise via an addition funnel over 1 hour. The reaction was quenched via addition of 0.1 N HCl (250 mL) and transferred to a separatory funnel containing EtOAc (600 mL). The layers were separated, and the organic layer was washed with 1N NaOH (2×100 mL each) and with brine (100 mL). The organic layer was dried over Na2SO4, filtered, and concentrated to afford 2-[(1R,2S)-5-chloro-2-methoxy-2,3-dihydro-1H-inden-1-yl]-1H-isoindole-1,3(2H)-dione (25.8 g, 96%) which was used without further purification in the next step.

Provenance & Evidence