Acetic Acid → 5-(2,6-difluorophenyl)-1H-pyrrolo[3,2-b]pyridine

HRID 1529332Notes

Reaction equation

HRID 1529332 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[N:14]=[C:13]([CH3:15])[C:12]([N+:16]([O-])=O)=[CH:11][CH:10]=1.[C:19](O)(=O)C>CN(C=O)C.CCOC(C)=O.C(O)C.[Fe]>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[N:14]=[C:13]2[CH:15]=[CH:19][NH:16][C:12]2=[CH:11][CH:10]=1

Participants

7

Reactant 2

HCID 176Acetic AcidHCID 679582356-(2,6-Difluorophenyl)-2-methyl-3-nitropyridine

Product 1

HCID 679601495-(2,6-difluorophenyl)-1H-pyrrolo[3,2-b]pyridineYield 72%

Reagents, catalysts & solvents 4

HCID 23925IronCatalystHCID 702EthanolSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
125 °C

Procedure

A solution of 6-(2,6-difluorophenyl)-2-methyl-3-nitropyridine (1.929 g, 7.71 mmol) in DMF (25 mL) was treated with n,n-dimethylformamide dimethyl acetal (1.331 mL, 10.02 mmol). The reaction was heated to 125° C. under N2. After 3 h, the reaction was cooled to 23° C., diluted with EtOAc (200 ml) and washed with brine (150 ml), dried over MgSO4, concentrated in vacuo, affording a purple solid that was carried forward to the next step without further manipulation. A suspension of that solid in ethanol (40.0 mL) and acetic acid (40 mL) was treated with iron powder—325 mesh (4.31 g, 77 mmol, Aldrich). The reaction was heated to 90° C. under N2. After 2 h, the reaction was cooled to 23° C., filtered through Celite, concentrated in vacuo and purified by silica gel chromatography (eluent: 0.5-3% MeOH/DCM), affording 5-(2,6-difluorophenyl)-1H-pyrrolo[3,2-b]pyridine (1.271 g, 72%).

Workup

  1. temperaturethe reaction was cooled to 23° C.
  2. washwashed with brine (150 ml)
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated in vacuo
  5. customaffording a purple solid
  6. temperatureThe reaction was heated to 90° C. under N2
  7. waitAfter 2 h
  8. temperaturethe reaction was cooled to 23° C.
  9. filtrationfiltered through Celite
  10. concentrationconcentrated in vacuo
  11. custompurified by silica gel chromatography (eluent: 0.5-3% MeOH/DCM)

Sources & evidence

ORD record
ord-34ae67e90ccc4ddf8ba273625cdeaf77
Source dataset
uspto-grants-2015_07
Patent number
US09090593B2

Reaction notes

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