Sulfuric Acid → N-(5-ethoxycarbonylmethyl-4,6-dimethylindolin-7-yl)-2,2-dimethylpropanamide

HRID 1744043Notes

Reaction equation

HRID 1744043 reaction equation
C([N:4]1[C:12]2[C:7](=[C:8]([CH3:27])[C:9]([CH2:21][C:22]([O:24][CH2:25][CH3:26])=[O:23])=[C:10]([CH3:20])[C:11]=2[NH:13][C:14](=[O:19])[C:15]([CH3:18])([CH3:17])[CH3:16])[CH2:6][CH2:5]1)(=O)C.[O-]CC.[Na+].S(=O)(=O)(O)O.[OH-].[Na+]>C(OCC)(=O)C.C(O)C.O>[CH2:25]([O:24][C:22]([CH2:21][C:9]1[C:8]([CH3:27])=[C:7]2[C:12](=[C:11]([NH:13][C:14](=[O:19])[C:15]([CH3:17])([CH3:16])[CH3:18])[C:10]=1[CH3:20])[NH:4][CH2:5][CH2:6]2)=[O:23])[CH3:26]

Participants

8

Reactant 4

HCID 1118Sulfuric AcidHCID 14798Sodium HydroxideHCID 2723922Sodium ethoxideHCID 15524344N-(1-acetyl-5-ethoxycarbonylmethyl-4,6-dimethylindolin-7-yl)-2,2-dimethylpropanamide

Product 1

HCID 12112203N-(5-ethoxycarbonylmethyl-4,6-dimethylindolin-7-yl)-2,2-dimethylpropanamideYield 104.9%

Reagents, catalysts & solvents 3

HCID 702EthanolSolvent2×HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of N-(1-acetyl-5-ethoxycarbonylmethyl-4,6-dimethylindolin-7-yl)-2,2-dimethylpropanamide obtained in Example 9 (3.5 g) and ethanol (35 ml) was added dropwise sodium ethoxide (20 wt % ethanol solution) while keeping the reaction temperature below 30° C., and the resulting mixture was refluxed for 1 hour. After cooling to 0–5° C., concentrated sulfuric acid (6.88 g, 7.5 equivalent) was added dropwise with stirring under cooling condition while keeping the reaction temperature below 30° C., and the resulting mixture was refluxed for 2 hours. Water (17.5 ml) was added to the reaction mixture, and ethanol was evaporated off in vacuo. To the residue obtained was added ethyl acetate (35 ml), and pH of the resulting mixture was adjusted with 25% aqueous sodium hydroxide solution (the aqueous layer was adjusted to pH 12–13), and the resulting mixture was partitioned between ethyl acetate and water. The separated organic layer was furthermore washed with water (35 ml). The washing and the aqueous layer separated above were combined and reextracted with ethyl acetate (35 ml). The extract and the organic layer separated above were combined and concentrated under reduced pressure to afford the title compound (3.26 g) as a crude product.

Workup

  1. customthe reaction temperature below 30° C.
  2. temperaturethe resulting mixture was refluxed for 1 hour
  3. temperatureAfter cooling to 0–5° C.
  4. temperatureunder cooling condition
  5. customthe reaction temperature below 30° C.
  6. temperaturethe resulting mixture was refluxed for 2 hours
  7. customwas evaporated off in vacuo
  8. customTo the residue obtained
  9. customwas partitioned between ethyl acetate and water
  10. washThe separated organic layer was furthermore washed with water (35 ml)
  11. customThe washing and the aqueous layer separated
  12. extractionThe extract
  13. customthe organic layer separated above
  14. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-e422c7a5c1ab471298c36b5c68dc23ec
Source dataset
uspto-grants-2006_03
Patent number
US07012147B2

Reaction notes

Loading…