Diethyl Malonate → 6-bromo-2,3-dihydro-1H-indol-2-one

HRID 1790390Notes

Reaction equation

HRID 1790390 reaction equation
[C:1]([O:9]CC)(=O)[CH2:2][C:3](OCC)=O.[H-].[Na+].BrC1[CH:20]=[CH:19][C:18]([Br:21])=[CH:17][C:16]=1[N+:22]([O-])=O.C(OCC)(=O)C>CS(C)=O>[CH2:2]1[C:1](=[O:9])[NH:22][C:16]2[CH:17]=[C:18]([Br:21])[CH:19]=[CH:20][C:3]1=2

Participants

6

Reactant 4

HCID 7761Diethyl MalonateHCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 770041,4-Dibromo-2-nitrobenzene

Product 1

HCID 27732896-bromo-2,3-dihydro-1H-indol-2-oneYield 85%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent2×

Procedure

Under ice cooling, diethyl malonate (500 g) was added dropwise into a suspension of sodium hydride (125 g) in dimethyl sulfoxide (800 ml). After the solution became homogeneous, the resultant mixture was heated to 100° C. and a solution of 2,5-dibromonitrobenzene (500 g) in dimethyl sulfoxide (400 ml) was added dropwise thereinto followed by stirring the resultant mixture at 100° C. for 5 hr. Then the reaction solution was diluted with ice water (2 l), mixed with ethyl acetate (8 l), and the layers were separated. The organic layer was washed successively with water (2 l) four times and brine and dried over anhydrous magnesium sulfate. After evaporating the solvent under reduced pressure, the residue was diluted with ethanol (2.5 l) followed by the addition of tin (380 g). Under ice cooling, conc. hydrochloric acid (1.5 l) was added dropwise into the reaction mixture. After the completion of the addition, the resultant mixture was heated under reflux for 3 hr and diluted with ice water (8 l). The resulting crystalline precipitates were collected by filtration, washed with water and hexane, and air dried at 50° C. for 24 hr to give the title compound (321 g) (yield: 84%).

Workup

  1. customthe layers were separated
  2. washThe organic layer was washed successively with water (2 l) four times and brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customAfter evaporating the solvent under reduced pressure
  5. additionthe residue was diluted with ethanol (2.5 l)
  6. additionfollowed by the addition of tin (380 g)
  7. additionUnder ice cooling, conc. hydrochloric acid (1.5 l) was added dropwise into the reaction mixture
  8. additionAfter the completion of the addition
  9. temperaturethe resultant mixture was heated
  10. temperatureunder reflux for 3 hr
  11. additiondiluted with ice water (8 l)
  12. customThe resulting crystalline precipitates
  13. filtrationwere collected by filtration
  14. washwashed with water and hexane, and air
  15. customdried at 50° C. for 24 hr

Sources & evidence

ORD record
ord-bf9294382bd446e1829cddfe2bb7bdae
Source dataset
uspto-grants-2006_07
Patent number
US07071201B2

Reaction notes

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