Tetrahydrofuran → 1-Ethyl-2-(hydroxymethyl)indole-6-carbonitrile

HRID 1532339Notes

Reaction equation

HRID 1532339 reaction equation
C(=O)(O)[O-].[Na+].O1CCCC1.[I-].[I-].[Ca+2].O.[BH4-].[Na+].[C:17]([C:19]1[CH:27]=[C:26]2[C:22]([CH:23]=[C:24]([C:30](OCC)=[O:31])[N:25]2[CH2:28][CH3:29])=[CH:21][CH:20]=1)#[N:18]>C(O)(=O)C>[CH2:28]([N:25]1[C:26]2[C:22](=[CH:21][CH:20]=[C:19]([C:17]#[N:18])[CH:27]=2)[CH:23]=[C:24]1[CH2:30][OH:31])[CH3:29]

Participants

7

Reactant 5

HCID 8028TetrahydrofuranHCID 516892Sodium BicarbonateHCID 4311764Sodium borohydrideHCID 17749104Calcium iodide--water (1/2/1)HCID 21251527Ethyl 6-cyano-1-ethylindole-2-carboxylate

Product 1

HCID 212515571-Ethyl-2-(hydroxymethyl)indole-6-carbonitrileYield 83.8%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
0 °C

Procedure

In a 1 l flask, 26.27 g of ethyl 6-cyano-1-ethylindole-2-carboxylate and 0.91 g of sodium bicarbonate were dissolved with 300 ml of tetrahydrofuran and then cooled to 0° C. To this mixture was added CaI2.H2O and then slowly added NaBH4. The reaction mixture was stirred while slowly warming from 0° C. to room temperature with stirring. After examined by TLC, ice and a catalytic amount of acetic acid were added thereto at 0° C. and the mixture was stirred. The reaction solution was evaporated to remove tetrahydrofuran, and the residue was diluted with water and extracted three times with ethyl acetate. The organic extracts were combined, dried over MgSO4 and then evaporated. The residue was purified with silica gel column chromatography [eluent: ethyl acetate/n-hexane(1:2)]. The fractions containing the desired product were combined and then evaporated to obtain 18.2 g of the title compound as a white solid.

Workup

  1. temperaturewhile slowly warming from 0° C. to room temperature
  2. stirringwith stirring
  3. stirringat 0° C. and the mixture was stirred
  4. customThe reaction solution was evaporated
  5. customto remove tetrahydrofuran
  6. additionthe residue was diluted with water
  7. extractionextracted three times with ethyl acetate
  8. dry with materialdried over MgSO4
  9. customevaporated
  10. customThe residue was purified with silica gel column chromatography [eluent: ethyl acetate/n-hexane(1:2)]
  11. additionThe fractions containing the desired product
  12. customevaporated

Sources & evidence

ORD record
ord-dc22b4fb862c47d99664dc319cad1a42
Source dataset
uspto-grants-2001_03
Patent number
US06201006B1

Reaction notes

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