Ethanol → 1H-Pyrrolo[2,3-c]pyridine-4-carboxylic acid, 1-(4-fluorophenyl)-, ethyl ester

HRID 1423024Notes

Reaction equation

HRID 1423024 reaction equation
Br[C:2]1[CH:7]=[N:6][CH:5]=[C:4]2[N:8]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[CH:9]=[CH:10][C:3]=12.CCN([CH2:23][CH3:24])CC.[C]=[O:26].[CH2:27]([OH:29])C>[Cl-].[NH4+].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2]>[CH2:23]([O:26][C:27]([C:2]1[C:3]2[CH:10]=[CH:9][N:8]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[C:4]=2[CH:5]=[N:6][CH:7]=1)=[O:29])[CH3:24]

Participants

7

Reactant 4

HCID 702EthanolHCID 8471TriethylamineHCID 67196157HCID 67196157, compoundHCID 178418416HCID 178418416, compound

Product 1

HCID 671974811H-Pyrrolo[2,3-c]pyridine-4-carboxylic acid, 1-(4-fluorophenyl)-, ethyl ester

Reagents, catalysts & solvents 2

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of 4-bromo-1-(4-fluorophenyl)-1H-pyrrolo[2,3-c]pyridine (820.0 mg, 2.82 mmol), Et3N (1.00 mL, 7.19 mmol), Pd[PhCN]2Cl2 (45 mg, 0.12 mmol), and dppf (155 mg, 0.28 mmol) in absolute ethanol (20 mL) is placed in a pressure reactor with stirring and placed under 15 bars of carbon monoxide and warmed at 140° C. After 2 hours, the pressure reactor is cooled to room temperature, returned to atmopheric pressure and opened. The reaction is diluted with ammonium chloride and extracted with EtOAc (3×25 mL). The combined organic layers are washed with brine (2×10 mL), dried over magnesium sulfate, filtered and concentrated. The crude material is purified by silica gel chromatography using a gradient of 5-25% EtOAc in hexanes to afford 1-(4-fluorophenyl)-1H-pyrrolo[2,3-c]pyridine-4-carboxylic acid ethyl ester.

Workup

  1. customis placed in a pressure reactor
  2. temperaturethe pressure reactor is cooled to room temperature
  3. extractionextracted with EtOAc (3×25 mL)
  4. washThe combined organic layers are washed with brine (2×10 mL)
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude material is purified by silica gel chromatography

Sources & evidence

ORD record
ord-c6cd9353e8994d06866bedc739d94f9e
Source dataset
uspto-grants-2015_01
Patent number
US08927550B2

Reaction notes

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