Methyl iodide → ethyl 1-methyl-1H-pyrrolo[2,3-c]pyridine-2-carboxylate

HRID 217169Notes

Reaction equation

HRID 217169 reaction equation
[H-].[Na+].[CH2:3]([O:5][C:6]([C:8]1[NH:16][C:11]2=[CH:12][N:13]=[CH:14][CH:15]=[C:10]2[CH:9]=1)=[O:7])[CH3:4].[CH3:17]I.[NH4+].[Cl-]>CN(C=O)C>[CH2:3]([O:5][C:6]([C:8]1[N:16]([CH3:17])[C:11]2=[CH:12][N:13]=[CH:14][CH:15]=[C:10]2[CH:9]=1)=[O:7])[CH3:4]

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 21819001ethyl 1H-pyrrolo[2,3-c]pyridine-2-carboxylate

Product 1

HCID 58117018ethyl 1-methyl-1H-pyrrolo[2,3-c]pyridine-2-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
20 °C

Procedure

NaH (60% dispersion in mineral oil, 51 mg, 1.26 mmol) was added to a solution of 1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid ethyl ester (200 mg, 1.05 mmol) in anhydrous DMF (10 mL) at 0° C. The mixture was stirred for 1 h, before being treated with MeI (79 μL, 1.26 mmol) and allowed to warm to 20° C. After 16 h, saturated aqueous NH4Cl (10 mL) was added, then the suspension was stirred vigorously for 1 h. The mixture was partitioned between H2O (10 mL) and EtOAc (30 mL), then the aqueous layer was extracted with EtOAc (3×20 mL). The combined organic extracts were washed with brine (20 mL), dried (MgSO4), filtered, and concentrated, then the residue was purified by flash chromatography (IH-EtOAc, 1:1) to provide 1-methyl-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid ethyl ester: δH (CDCl3): 1.45 (t, 3H), 4.20 (s, 3H), 4.42 (q, 2H), 7.25 (s, 1H), 7.58 (d, 1H), 8.36 (d, 1H), 8.95 (s, 1H). A solution of this ester (36 mg, 180 μmol) in EtOH (3 mL) was treated with 2 M NaOH (270 μL, 540 μmol), then the mixture was stirred at 60° C. for 4 h. On cooling to ambient temperature, the mixture was treated dropwise with dilute AcOH to adjust the pH to 4. The resulting suspension was allowed to stand at ambient temperature for 7 d, then the precipitated solid was collected, washed with H2O, and dried to furnish the title compound: δH(CD3OD): 4.23 (s, 3H), 7.20 (s, 1H), 8.01 (d, 1H), 8.17 (d, 1H), 9.12 (s, 1H).

Workup

  1. waitAfter 16 h
  2. stirringthe suspension was stirred vigorously for 1 h
  3. customThe mixture was partitioned between H2O (10 mL) and EtOAc (30 mL)
  4. extractionthe aqueous layer was extracted with EtOAc (3×20 mL)
  5. washThe combined organic extracts were washed with brine (20 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customthe residue was purified by flash chromatography (IH-EtOAc, 1:1)

Sources & evidence

ORD record
ord-39020022e9f744d183ceb2c0ebcb6b2d
Source dataset
uspto-grants-2012_06
Patent number
US08193359B2

Reaction notes

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