Ammonium Chloride → Ethyl 5-chloro-1H-pyrrolo[3,2-b]pyridine-2-carboxylate

HRID 1693347Notes

Reaction equation

HRID 1693347 reaction equation
[CH2:1]([O:3][C:4](=[O:18])[C:5](=O)[CH2:6][C:7]1[N:12]=[C:11]([Cl:13])[CH:10]=[CH:9][C:8]=1[N+:14]([O-])=O)[CH3:2].[Cl-].[NH4+]>C1COCC1.C(O)C.[Fe]>[CH2:1]([O:3][C:4]([C:5]1[NH:14][C:8]2[C:7](=[N:12][C:11]([Cl:13])=[CH:10][CH:9]=2)[CH:6]=1)=[O:18])[CH3:2]

Participants

6

Reactant 2

HCID 25517Ammonium ChlorideHCID 59753627HCID 59753627, compound

Product 1

HCID 45480460Ethyl 5-chloro-1H-pyrrolo[3,2-b]pyridine-2-carboxylate

Reagents, catalysts & solvents 3

HCID 23925IronCatalystHCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-(2-chloro-5-nitropyridin-6-yl)-2-oxopropionic acid ethyl ester (Preparation 4, 1.53 g, 5.6 mmol) in THF (65 mL) and ethanol (30 mL) was added saturated aqueous ammonium chloride solution (30 mL) and the suspension was vigorously stirred at rt. Iron powder (1.95 g, 34.8 mmol) was added portionwise and the mixture was heated under reflux for 2 h then allowed to cool prior to filtration through a celite plug, and washed through with warm THF. The mixture was concentrated under reduced pressure to give an aqueous suspension, which was filtered through a sinter, washing with water. The wet solid was washed with methanol and dried. The residue was adsorbed onto silica gel and purified via flash chromatography eluting with ethyl acetate/hexane (1:19) to give the title compound as a white solid. δH (CD3OD): 1.42 (3H, t, 7.03 Hz), 4.42 (2H, q, 7.32 Hz), 7.15 (1H, s), 7.30 (1H, d, 8.79 Hz), 7.89 (1H, d, 8.35 Hz); m/z (ES+)=225.03 [M+H]+; RT=3.32 min.

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 2 h
  3. temperatureto cool
  4. filtrationto filtration through a celite plug
  5. washwashed through with warm THF
  6. concentrationThe mixture was concentrated under reduced pressure
  7. customto give an aqueous suspension, which
  8. filtrationwas filtered through a sinter
  9. washwashing with water
  10. washThe wet solid was washed with methanol
  11. customdried
  12. custompurified via flash chromatography
  13. washeluting with ethyl acetate/hexane (1:19)

Sources & evidence

ORD record
ord-4b6223b298564d7e9857cf9fb72e7523
Source dataset
uspto-grants-2012_04
Patent number
US08158622B2

Reaction notes

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