Chlorosuccinimide → Ethyl 4-chloro-2-(2-fluoroethyl)-5-methoxy-1-oxoindane-2-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a solution of ethyl 2-(2-fluoroethyl)-5-methoxy-1-oxoindane-2-carboxylate (44.6 g, 159 mmol) in DMF (159 mL) was added N-chlorosuccinimide (23.4 g, 175 mmol) in portions. The solution was heated at 50° C. and the reaction was monitored periodically by NMR analysis of aliquots. After 6 hours, the reaction was approximately 80% complete by NMR analysis. The reaction mixture was allowed to cool to room temperature and stand overnight. After reheating to 50° C., additional N-chlorosuccinimide (2.12 g, 15.9 mmol) was added. Monitoring by NMR was continued, and after 4.5 hours another portion of N-chlorosuccinimide (2.12 g, 15.9 mmol) was added. After another 3 hours, the reaction was allowed to cool to room temperature and stand overnight. Most of the DMF was removed by evaporation at reduced pressure and the residue was partitioned between EtOAc and water. The organic phase was washed with water (4 times) and brine and dried over Na2SO4. Filtration and removal of the solvent under reduced pressure gave crude ethyl 4-chloro-2-(2-fluoroethyl)-5-methoxy-1-oxoindane-2-carboxylate. This material was used in the next step without purification.

Provenance & Evidence