Dimethylformamide → methyl 1H-indole-4-carboxylate

HRID 2388582Notes

Reaction equation

HRID 2388582 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][C:6](C(O)=O)=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[C:13](=[O:16])([O-])[OH:14].[Na+].CI.[CH3:20]N(C=O)C>C(OCC)(=O)C.O>[NH:1]1[C:9]2[CH:8]=[CH:7][CH:6]=[C:5]([C:13]([O:14][CH3:20])=[O:16])[C:4]=2[CH:3]=[CH:2]1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 6328Methyl iodideHCID 742801H-Indole-5-Carboxylic AcidHCID 516892Sodium Bicarbonate

Product 1

HCID 2733668methyl 1H-indole-4-carboxylateYield 99%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a 100 mL round bottomed flask was added, indole-5-carboxylic acid (3.57 g, 22.2 mmol), powdered sodium hydrogen carbonate (5.95 g, 70.83 mmol), methyl iodide (5.95 mL, 95.6 mmol) and DMF (25 mL). The mixture was stirred for 72 h under an atmosphere of nitrogen, whereupon water (20 mL) and ethyl acetate (40 mL) was added. The phases were then partitioned and the aqueous phase extracted with ethyl acetate (40 mL). The combined organics were washed with aqueous sodium hydrogen carbonate, dried (sodium sulfate) and concentrated to furnish a white solid (3.88 g, 99%). 1H NMR (400 MHz, Acetone d6, δ in ppm) 10.61 (br s, 1H), 8.38 (s, 1H), 7.81 (dd, J=8.6 and 1.5 Hz), 7.51 (1H, d, J=8.6 Hz), 7.46 (m, 1H), 6.65-6.63 (1H, m) and 3.87 (3H, s).

Workup

  1. additionTo a 100 mL round bottomed flask was added
  2. additionwas added
  3. customThe phases were then partitioned
  4. extractionthe aqueous phase extracted with ethyl acetate (40 mL)
  5. washThe combined organics were washed with aqueous sodium hydrogen carbonate
  6. dry with materialdried (sodium sulfate)
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-fa5e2dc02ef641208d8dfc722e62b262
Source dataset
uspto-grants-2012_09
Patent number
US08268872B2

Reaction notes

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