Sodium hydride → Ethyl 3-(5-hydroxy-1-methyl-1H-indol-3-yl)-2-isopropoxypropionate

HRID 1985426Notes

Reaction equation

HRID 1985426 reaction equation
C(P([CH:7]([CH:13]([CH3:15])C)[C:8]([O:10][CH2:11][CH3:12])=[O:9])(CC)=O)C.[H-].[Na+].C([O:25][C:26]1[CH:27]=[C:28]2[C:32](=[CH:33][CH:34]=1)[N:31]([CH3:35])[CH:30]=C2C=O)C1C=CC=CC=1.[Cl-].[NH4+]>O1CCCC1.CN(C)C=O.O>[OH:25][C:26]1[CH:34]=[C:33]2[C:32](=[CH:28][CH:27]=1)[N:31]([CH3:35])[CH:30]=[C:15]2[CH2:13][CH:7]([O:25][CH:26]([CH3:27])[CH3:34])[C:8]([O:10][CH2:11][CH3:12])=[O:9]

Participants

8

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 122838545-Benzyloxy-1-methylindole-3-carboxaldehydeHCID 22494181Ethyl 2-(diethylphosphoryl)-2-isopropylacetate

Product 1

HCID 22926993Ethyl 3-(5-hydroxy-1-methyl-1H-indol-3-yl)-2-isopropoxypropionateYield 173.8%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

3.2 g of Ethyl 2-(diethylphosphoryl)-2-isopropylacetate was dissolved in 25 ml of tetrahydrofuran, and 0.44 g of 60% sodium hydride was added under ice-cooling, and stirring was continued for 20 minutes under ice-cooling. The reaction solution was treated with a solution of 2 g of 5-benzyloxy-1-methyl-1H-indol-3-aldehyde in 5 ml of tetrahydrofuran and 5 ml of N,N-dimethylformamide, and stirred at 50° C. for one hour and then at room temperature for 16 hours. The reaction solution was cooled with ice, treated with water and ammonium chloride solution, and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and evaporated. The residue was subjected to silica gel column chromatography, and the fraction eluting with 20% ethylacetate-hexane was evaporated and the residue was dissolved in 10 ml of ethanol. 0.6 g of 10% Palladium carbon was added to this solution, the atmosphere was replaced with hydrogen, and the mixture was stirred at room temperature for 24 hours. The reaction atmosphere was replaced with nitrogen, the catalyst was filtered off, and the solvent was evaporated. The residue was subjected to silica gel column chromatography (30% ethyl acetate hexane), to give 2 g of the title compound.

Workup

  1. temperaturecooling
  2. temperaturecooling
  3. stirringstirred at 50° C. for one hour
  4. waitat room temperature for 16 hours
  5. temperatureThe reaction solution was cooled with ice
  6. extractionextracted with ethyl acetate
  7. washThe organic layer was washed with saturated brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. customevaporated
  10. washthe fraction eluting with 20% ethylacetate-hexane
  11. customwas evaporated
  12. dissolutionthe residue was dissolved in 10 ml of ethanol
  13. addition0.6 g of 10% Palladium carbon was added to this solution
  14. stirringthe mixture was stirred at room temperature for 24 hours
  15. customThe reaction atmosphere
  16. filtrationthe catalyst was filtered off
  17. customthe solvent was evaporated

Sources & evidence

ORD record
ord-6c28428224af4d7dbc446d1a22e58779
Source dataset
uspto-grants-2009_06
Patent number
US07544835B2

Reaction notes

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