Dimethylformamide → 6-Formyl-4-methoxy-quinoline-3-carboxylic acid amide

HRID 1297612Notes

Reaction equation

HRID 1297612 reaction equation
I[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][C:6]([C:12]([NH2:14])=[O:13])=[C:5]2[O:15][CH3:16].C(N(CC)CC)C.C([SiH](CCCCCC)CCCCCC)CCCCC.CN(C)[CH:45]=[O:46]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C(C2C=CC=CC=2)CCP)C=CC=CC=1>[CH:45]([C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][C:6]([C:12]([NH2:14])=[O:13])=[C:5]2[O:15][CH3:16])=[O:46]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 76231CID 76231HCID 688249156-Iodo-4-methoxy-quinoline-3-carboxylic acid amide

Product 1

HCID 585858016-Formyl-4-methoxy-quinoline-3-carboxylic acid amideYield 64%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 53436545Diphenylpropyl phosphineCatalyst

Procedure

A mixture of 6-iodo-4-methoxy-quinoline-3-carboxylic acid amide (example 1d) (1.3 g, 4 mmol), triethylamine (1.4 mL, 3.5 mmol), diphenylpropylphosphine (dpp, 45 uL, 0.2 mmol) and palladium(II) acetate (45 mg, 0.2 mmol) in dry N,N-dimethylformamide (30 mL) in pressure tube was stirred under carbon monoxide at 75 psi at room temperature for 10 min. After addition of trihexylsilane (0.2.9 mL, 8 mmol), the mixture was then stirred under carbon monoxide at 75 psi at 80° C. for 4 h. The reaction was allowed to cool to 25° C. and then extracted with methylene chloride (2×150 mL). The combined organic layers were successively washed with water (3×50 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 70-230 mesh, 20%-100% ethyl acetate in hexanes in 30 min) afforded 6-formyl-4-methoxy-quinoline-3-carboxylic acid amide (0.58 g, 64%) as a light yellow solid.

Workup

  1. stirringthe mixture was then stirred under carbon monoxide at 75 psi at 80° C. for 4 h
  2. temperatureto cool to 25° C.
  3. extractionextracted with methylene chloride (2×150 mL)
  4. washThe combined organic layers were successively washed with water (3×50 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-b3e23ac9b6c54352aa4db87b4b063118
Source dataset
uspto-grants-2007_07
Patent number
US07250515B2

Reaction notes

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