Trifluoroacetic acid → 1H-pyrrolo[3,2-c]pyridine-2-carbaldehyde

HRID 1865186Notes

Reaction equation

HRID 1865186 reaction equation
C(O)(C(F)(F)F)=O.CC(OC([N:15]1[C:23]2[CH:22]=[CH:21][N:20]=[CH:19][C:18]=2[CH:17]=[C:16]1[CH:24]=[O:25])=O)(C)C>ClCCl>[NH:15]1[C:23]2[CH:22]=[CH:21][N:20]=[CH:19][C:18]=2[CH:17]=[C:16]1[CH:24]=[O:25]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86598690tert-Butyl 2-formyl-1H-pyrrolo[3,2-c]pyridine-1-carboxylate

Product 1

HCID 450795071H-pyrrolo[3,2-c]pyridine-2-carbaldehydeYield 75.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Add to a solution of 2-(diethoxymethyl)-1H-pyrrolo[3,2-c]pyridine-1-carboxylic acid 1,1-dimethylethyl ester (8b-1, 9.8 g, 30.6 mmol) in 100 ml THF, 6 ml of concentrated HCl. Stir the reaction mixture at room temperature for 20 h, basify with saturated sodium bicarbonate solution, pour into EtOAc, wash with saturated sodium bicarbonate and brine, dry the organic phase over MgSO4, filter, and concentrate to give a mixture of 2-formyl-1H-pyrrolo[3,2-c]pyridine-1-carboxylic acid 1,1-dimethylethyl ester and 1H-pyrrolo[3,2-c]pyridine-2-carboxaldehyde 9b-1 as a solid. Separate the mixture by flash chromatography (silica, 1-3% MeOH/CH2Cl2) to give 2-formyl-1H-pyrrolo[3,2-c]pyridine-1-carboxylic acid 1,1-dimethylethyl ester (5.0 g) as an oil and 1H-pyrrolo[3,2-c]pyridine-2-carboxaldehyde 9b-1 (1.0 g) as a tan solid. Add TFA (5.0 mL) dropwise to a solution of 2-formyl-1H-pyrrolo[3,2-c]pyridine-1-carboxylic acid 1,1-dimethylethyl ester (5.0 g, 20.3 mmol) in 250 ml dichloromethane. Heat the reaction mixture at reflux for 3 hours, concentrate, dilute the residue with 300 ml EtOAc, wash with saturated sodium bicarbonate solution (3×) and brine, dry the organic phase (MgSO4), filter and concentrate to yield 1H-pyrrolo[3,2-c]pyridine-2-carboxaldehyde 9b-1 (2.24 g) as a pure solid.

Workup

  1. temperatureHeat the reaction mixture
  2. temperatureat reflux for 3 hours
  3. concentrationconcentrate
  4. additiondilute the residue with 300 ml EtOAc
  5. washwash with saturated sodium bicarbonate solution (3×) and brine
  6. dry with materialdry the organic phase (MgSO4)
  7. filtrationfilter
  8. concentrationconcentrate

Sources & evidence

ORD record
ord-f0ccc4e5e5a84879b580aee776621e64
Source dataset
uspto-grants-2009_12
Patent number
US07626027B2

Reaction notes

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