Hydrochloric Acid → 2-[(E)-1-(1,2-dimethyl-5-methoxy-3-indolyl)ethylidene]-3-isopropylidene succinic anhydride

HRID 1708603Notes

Reaction equation

HRID 1708603 reaction equation
[CH:1](NC(C)C)(C)C.[C:8]1(=O)[O:21][C:14](C)([CH:15]([CH2:18][CH3:19])CC)[O:13][C:11](=[O:12])[CH2:10][CH2:9]1.C([C:26]1[C:34]2[C:29](=[CH:30][CH:31]=[C:32]([O:35][CH3:36])[CH:33]=2)[N:28]([CH3:37])[C:27]=1[CH3:38])(=O)C.Cl>O1CCCC1.C([Li])CCC.C(Cl)(Cl)Cl>[CH3:37][N:28]1[C:29]2[C:34](=[CH:33][C:32]([O:35][CH3:36])=[CH:31][CH:30]=2)[C:26](/[C:18](=[C:15]2/[C:14]([O:13][C:11](=[O:12])[C:10]/2=[C:9]([CH3:8])[CH3:1])=[O:21])/[CH3:19])=[C:27]1[CH3:38]

Participants

8

Reactant 4

HCID 313Hydrochloric Acid2×HCID 7912DiisopropylamineHCID 7447201-(5-Methoxy-1,2-dimethyl-1H-indol-3-yl)ethanoneHCID 54162692Diethylisopropylidene succinate

Product 1

HCID 547687672-[(E)-1-(1,2-dimethyl-5-methoxy-3-indolyl)ethylidene]-3-isopropylidene succinic anhydrideYield 5%

Reagents, catalysts & solvents 3

HCID 6212ChloroformSolventHCID 8028TetrahydrofuranSolventHCID 178418339ButyllithiumSolvent

Procedure

To a solution obtained by dissolving 76 g of diisopropylamine in 750 ml of tetrahydrofuran, 350 ml of n-butyllithium was added at low temperatures (-10°~-40° C.), and 91 g of diethylisopropylidene succinate obtained in Reference Example 1 (4) and 81 g of 3-acetyl-5-methoxy-1,2-dimethylindole were added dropwise thereto in 30 minutes with stirring. After reacting for further 8 hours with stirring, the reaction solution was made acidic by pouring 1050 ml of 10% HCl thereinto, followed by extraction with 1.5 liters of ethyl acetate. The resulting organic layer was concentrated. To the residue, 1.85 liters of 5 w/v% ethanolic potassium hydroxide was added to carry out the reaction for 15 hours under reflux. After the reaction, the reaction solution was made acidic with HCl. A precipitate produced was dissolved in chloroform. After removing the solvent from the resulting chloroform solution by distillation, acetyl chloride was added to the residue to carry out a ring closing reaction. The residue was purified by column chromatography (filler: Wakogel C-300, eluent: a mixed solvent of n-hexane and ethyl acetate) to give pale yellow crystals of 2-[(E)-1-(1,2-dimethyl-5-methoxy-3-indolyl)ethylidene]-3-isopropylidene succinic anhydride of the formula: ##STR30## wherein Me is methyl, in yield of 5%.

Workup

  1. customTo a solution obtained
  2. additionwere added dropwise
  3. waitAfter reacting for further 8 hours
  4. stirringwith stirring
  5. extractionfollowed by extraction with 1.5 liters of ethyl acetate
  6. concentrationThe resulting organic layer was concentrated
  7. additionTo the residue, 1.85 liters of 5 w/v% ethanolic potassium hydroxide was added
  8. customthe reaction for 15 hours
  9. temperatureunder reflux
  10. customAfter the reaction
  11. customA precipitate produced
  12. customAfter removing the solvent from the resulting chloroform solution
  13. distillationby distillation, acetyl chloride
  14. additionwas added to the residue
  15. customreaction
  16. customThe residue was purified by column chromatography (filler

Sources & evidence

ORD record
ord-5ce58f3702e54a4eb20d7f11795b8dff
Source dataset
uspto-grants-1994_10
Patent number
US05359085

Reaction notes

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