1-Chloroethyl chloroformate → 4-Ethenyl-2,3-dihydro-1H-isoindole

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Reaction Steps

A solution of 2-benzyl-4-vinylisoindoline (58 mmol) in 1,2-dichloroethane (150 mL) was placed in a 1 L round-bottom flask under nitrogen. An addition funnel containing a solution of 1-chloroethyl chloroformate (7.51 mL, 69.6 mmol) in 1,2-dichloroethane was attached to the reaction flask. The reaction flask was cooled in an ice bath, and the contents of the addition funnel were added dropwise over 20 min, keeping the internal reaction temperature <5° C. After the addition was complete, the reaction flask was allowed to warm to RT, then heated to reflux for 45 min. The contents of the reaction flask were cooled to RT, then the solvent was removed by evaporation. MeOH (200 mL) was added, and the contents of the reaction flask were heated to reflux for 30 min. The reaction flask was cooled, and the solvent removed by evaporation. Water (200 mL) was added, and the resulting mixture washed with EtOAc (2×250 mL). The aqueous layer was made basic with 2N NaOH then extracted with methylene chloride (4×250 mL). The combined organic extracts were dried with anhydrous Na2SO4, filtered and the filtrate evaporated. The remaining residue was subjected to flash column chromatography eluting with methylene chloride/MeOH/NH4OH 97/3/0.3 to 95/5/0.5. Evaporation of fractions gave the title compound as a brown oil, 6.00 g (41.4 mmol, 71% yield for two steps). LRMS (ESI) m/z 146 [(M+H)+; calcd for C10H12N: 146].

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