5-chloro-1H-indole-2,3-dione → 5-Chloro-3-hydroxy-3-(4-methoxyphenyl)-1,3-dihydro-2H-indol-2-one

HRID 2102653Notes

Reaction equation

HRID 2102653 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([Mg]Br)=[CH:5][CH:4]=1.[Cl:11][C:12]1[CH:13]=[C:14]2[C:18](=[CH:19][CH:20]=1)[NH:17][C:16](=[O:21])[C:15]2=[O:22]>O1CCCC1>[Cl:11][C:12]1[CH:13]=[C:14]2[C:18](=[CH:19][CH:20]=1)[NH:17][C:16](=[O:21])[C:15]2([OH:22])[C:6]1[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=1

Participants

4

Reactant 2

HCID 872035-chloro-1H-indole-2,3-dioneHCID 178491912HCID 178491912, compound

Product 1

HCID 225609075-Chloro-3-hydroxy-3-(4-methoxyphenyl)-1,3-dihydro-2H-indol-2-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-25 °C

Procedure

A solution of 4-methoxyphenyl magnesium bromide in tetrahydrofuran (0.5 M, 50 mL, 25 mmol) (Aldrich) was added dropwise to a suspension of 5-chloroisatin (1.82 g, 10 mmol) (Avocado) in tetrahydrofuran (20 mL) under argon with cooling in a −25° C. bath and magnetic stirring at such a rate that reaction temperature was kept below −10° C. (approximately 30 minutes). Cooling bath was then removed and mixture allowed to warm to room temperature. After stirring for an additional 1 hour, 15% aqueous ammonium chloride solution (50 mL) was added and mixture extracted with ethyl acetate (2×75 mL). Ethyl acetate layers were then washed with water (75 mL), brine (75 mL), combined, dried (MgSO4), filtered and concentrated. Residue was stirred in dichloromethane (100 mL) at room temperature for 30 minutes and filtered to give crude rac-5-chloro-3-hydroxy-3-(4-methoxy-phenyl)-1,3-dihydro-indol-2-one as a white powder. (Yield 2.57 g, 88.7%).

Workup

  1. customthat reaction temperature
  2. customwas kept below −10° C.
  3. custom(approximately 30 minutes)
  4. temperatureCooling bath
  5. customwas then removed
  6. temperatureto warm to room temperature
  7. stirringAfter stirring for an additional 1 hour
  8. addition15% aqueous ammonium chloride solution (50 mL) was added
  9. extractionmixture extracted with ethyl acetate (2×75 mL)
  10. washEthyl acetate layers were then washed with water (75 mL), brine (75 mL)
  11. dry with materialdried (MgSO4)
  12. filtrationfiltered
  13. concentrationconcentrated
  14. stirringResidue was stirred in dichloromethane (100 mL) at room temperature for 30 minutes
  15. filtrationfiltered

Sources & evidence

ORD record
ord-91cda980f6434b6ea96b3b3d21a732a5
Source dataset
uspto-grants-2009_08
Patent number
US07576082B2

Reaction notes

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