Potassium Hydroxide → Methyl 2-(1H-pyrrolo[2,3-b]pyridin-3-yl)acetate

HRID 1754474Notes

Reaction equation

HRID 1754474 reaction equation
[CH3:1][O:2][C:3](=[O:15])[C:4](=O)[C:5]1[C:13]2[C:8](=[N:9][CH:10]=[CH:11][CH:12]=2)[NH:7][CH:6]=1.[OH-].[K+]>O.NN>[CH3:1][O:2][C:3](=[O:15])[CH2:4][C:5]1[C:13]2[C:8](=[N:9][CH:10]=[CH:11][CH:12]=2)[NH:7][CH:6]=1

Participants

4

Reactant 2

HCID 14797Potassium HydroxideHCID 6028556Methyl 7-azaindole-3-glyoxylate

Product 1

HCID 25067325Methyl 2-(1H-pyrrolo[2,3-b]pyridin-3-yl)acetate

Reagents, catalysts & solvents 1

HCID 24654Hydrazine hydrate (1:1)Solvent

Conditions

Temperature
80 °C

Procedure

81 b) A mixture of oxo-(1H-pyrrolo[2,3-b]pyridine-3-yl)-acetic acid methyl ester (0.300 g, 1.47 mmol) is refluxed in hydrazine monohydrate (10 mL) for 1 hour to give a solution. KOH pellets (0.300 g, 5.35 mmol) are added and reflux is continued for 1 hour. The reaction mixture is evaporated to dryness in vacuo. To the residue is added dry MeOH (10 mL) and the solution is cooled in an ice bath. Concentrated H2SO4 (0.5 mL) is carefully added and the reaction mixture is refluxed at 80° C. for 1 hour. The reaction mixture is evaporated to dryness in vacuo, then partitioned between saturated NaHCO3 aqueous and EtOAc. The EtOAc layer is separated and the aqueous phase is extracted with a further portion of EtOAc. The organics are combined, dried (Na2SO4) and evaporated in vacuo. The crude product is purified by flash chromatography with a pre-packed Isolute™ silica column, eluting with 1:8 EtOAc/iso-hexane-neat EtOAc gradient to afford (1H-pyrrolo[2,3-b]pyridine-3-yl)-acetic acid methyl ester; MH+=191.

Workup

  1. customto give a solution
  2. additionare added
  3. temperaturereflux
  4. customThe reaction mixture is evaporated to dryness in vacuo
  5. additionTo the residue is added dry MeOH (10 mL)
  6. temperaturethe solution is cooled in an ice bath
  7. additionConcentrated H2SO4 (0.5 mL) is carefully added
  8. customThe reaction mixture is evaporated to dryness in vacuo
  9. custompartitioned between saturated NaHCO3 aqueous and EtOAc
  10. customThe EtOAc layer is separated
  11. extractionthe aqueous phase is extracted with a further portion of EtOAc
  12. dry with materialdried (Na2SO4)
  13. customevaporated in vacuo
  14. customThe crude product is purified by flash chromatography with a pre-packed Isolute™ silica column
  15. washeluting with 1:8 EtOAc/iso-hexane-neat EtOAc gradient

Sources & evidence

ORD record
ord-cb3ed945339b4b72bd661ec63ba7dfe8
Source dataset
uspto-grants-2015_10
Patent number
US09169251B2

Reaction notes

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