Dimethylformamide → 6-Formyl-4-methoxy-3-(5-methyl-oxazol-2-yl)-quinoline

HRID 1297638Notes

Reaction equation

HRID 1297638 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]1[O:13][C:14]([CH3:17])=[CH:15][N:16]=1)=[C:5]2[O:18][CH3:19].C1(C(C2C=CC=CC=2)CCP)C=CC=CC=1.C([SiH](CCCCCC)CCCCCC)CCCCC.CN(C)[CH:57]=[O:58]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:57]([C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][C:6]([C:12]1[O:13][C:14]([CH3:17])=[CH:15][N:16]=1)=[C:5]2[O:18][CH3:19])=[O:58]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 76231CID 76231HCID 53436545Diphenylpropyl phosphineHCID 585857786-Iodo-4-methoxy-3-(5-methyl-oxazol-2-yl)-quinoline

Product 1

HCID 585858616-Formyl-4-methoxy-3-(5-methyl-oxazol-2-yl)-quinolineYield 40%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Procedure

A mixture of 6-iodo-4-methoxy-3-(5-methyl-oxazol-2-yl)-quinoline (example 16c) (492 mg, 1.34 mmol), trethylamine (0.46 mL, 3.35 mmol), diphenylpropylphosphine (dpp, 31 uL, 0.13 mmol) and palladium(II) acetate (31 mg, 0.13 mmol) in dry N,N-dimethylformamide (20 mL) in pressure tube was stirred under carbon monoxide at 75 psi at room temperature for 10 min. After addition of trihexylsilane (1.01 mL, 2.68 mmol), the mixture was then stirred under carbon monoxide at 75 psi at 80° C. for 5 h. The reaction was allowed to cool to 25° C. and then extracted with ethyl acetate (2×100 mL). The combined organic layers were successively washed with a saturated aqueous sodium bicarbonate solution (3×50 mL) and water (3×50 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 70-230 mesh, 0%-50% ethyl acetate in hexanes in 30 min) afforded 6-formyl-4-methoxy-3-(5-methyl-oxazol-2-yl)-quinoline (144 mg, 40%) as a white solid. LC-MS m/e 269 (MH+).

Workup

  1. stirringthe mixture was then stirred under carbon monoxide at 75 psi at 80° C. for 5 h
  2. temperatureto cool to 25° C.
  3. extractionextracted with ethyl acetate (2×100 mL)
  4. washThe combined organic layers were successively washed with a saturated aqueous sodium bicarbonate solution (3×50 mL) and water (3×50 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-7050115c10484c39b2157872993d24ae
Source dataset
uspto-grants-2007_07
Patent number
US07250515B2

Reaction notes

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