Hydrochloric Acid → 5-methoxy-3-methyl-1H-indole

HRID 1165486Notes

Reaction equation

HRID 1165486 reaction equation
[H-].[Na+].OC1C(C)=CC([C:11]2[NH:12][C:13]3[C:18]([C:19]=2[CH3:20])=[CH:17][C:16]([O:21][CH3:22])=[CH:15][CH:14]=3)=CC=1C.C1(=O)OC(=O)CC1.Cl>CN(C)C=O.C(OCC)(=O)C.C1C=CC=CC=1.O>[CH3:22][O:21][C:16]1[CH:17]=[C:18]2[C:13](=[CH:14][CH:15]=1)[NH:12][CH:11]=[C:19]2[CH3:20]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 7922Succinic anhydrideHCID 24758Sodium hydrideHCID 1284802-(4-Hydroxy-3,5-dimethylphenyl)-5-methoxy-3-methylindole

Product 1

HCID 111374445-methoxy-3-methyl-1H-indole

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolvent3×HCID 21583983Benzene ethyl acetateSolvent

Conditions

Temperature
50 °C

Procedure

In 30 ml of dry dimethylformamide was dissolved 0.88 g of 60% sodium hydride in oil. With ice cooling and stirring, a solution of 5.62 g of 2-(4-hydroxy-3,5-dimethylphenyl)-5-methoxy-3-methylindole in dry dimethylformamide was added dropwise. After the addition, the mixture was stirred further for 1 hour. A solution of 2.2 g of succinic anhydride in dimethylformamide was added dropwise to the resulting solution. After the addition, the mixture was stirred at room temperature for 2 hours, then heated at 50° C. for 30 minutes, and further stirred at room temperature for 3 hours. The reaction solution was poured into water, acidified with dilute hydrochloric acid, and extracted with ethyl acetate. The organic layer was washed with water, and extracted with aqueous sodium bicarbonate solution. The extracted aqueous layer was acidified with dilute hydrochloric acid, and extracted with 100 ml of ethyl acetate three times. The organic layers were washed and dried, and the solvent was evaporated under reduced pressure to give a crystalline residue. Rerrystallization of the residue from ethyl acetate/benzene gave 2-4-(3-carboxy- propionyloxy)-3,5-dimethylphenyl]-5-methoxy-3-methylindole.

Workup

  1. additionAfter the addition
  2. stirringthe mixture was stirred further for 1 hour
  3. additionAfter the addition
  4. stirringthe mixture was stirred at room temperature for 2 hours
  5. stirringfurther stirred at room temperature for 3 hours
  6. extractionextracted with ethyl acetate
  7. washThe organic layer was washed with water
  8. extractionextracted with aqueous sodium bicarbonate solution
  9. extractionextracted with 100 ml of ethyl acetate three times
  10. washThe organic layers were washed
  11. customdried
  12. customthe solvent was evaporated under reduced pressure
  13. customto give a crystalline residue

Sources & evidence

ORD record
ord-43d35940838b4a5c97093b6a83476044
Source dataset
uspto-grants-1990_03
Patent number
US04910216

Reaction notes

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