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

HRID 859244Notes

Reaction equation

HRID 859244 reaction equation
[F:1][CH2:2][CH2:3][C:4]1([C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH2:12][C:11]2[C:6](=[CH:7][CH:8]=[C:9]([O:13][CH3:14])[CH:10]=2)[C:5]1=[O:15].[Cl:21]N1C(=O)CCC1=O>CN(C=O)C>[Cl:21][C:10]1[C:9]([O:13][CH3:14])=[CH:8][CH:7]=[C:6]2[C:11]=1[CH2:12][C:4]([CH2:3][CH2:2][F:1])([C:16]([O:18][CH2:19][CH3:20])=[O:17])[C:5]2=[O:15]

Participants

4

Reactant 2

HCID 31398Chlorosuccinimide3×HCID 16726730Ethyl 2-(2-fluoroethyl)-5-methoxy-1-oxoindane-2-carboxylate

Product 1

HCID 16726731Ethyl 4-chloro-2-(2-fluoroethyl)-5-methoxy-1-oxoindane-2-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

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.

Workup

  1. temperatureto cool to room temperature
  2. waitstand overnight
  3. customAfter reheating to 50° C.
  4. waitAfter another 3 hours
  5. temperatureto cool to room temperature
  6. waitstand overnight
  7. customMost of the DMF was removed by evaporation at reduced pressure
  8. customthe residue was partitioned between EtOAc and water
  9. washThe organic phase was washed with water (4 times) and brine
  10. dry with materialdried over Na2SO4
  11. filtrationFiltration and removal of the solvent under reduced pressure

Sources & evidence

ORD record
ord-eac1b06d88d245e396d9ff0bbec04f81
Source dataset
uspto-grants-2006_12
Patent number
US07151196B2

Reaction notes

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