Butane → 4-(4-Phenoxy-quinazolin-6-yl)benzaldehyde

HRID 983880Notes

Reaction equation

HRID 983880 reaction equation
CCCC.I[C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][CH:15]=1)[N:12]=[CH:11][N:10]=[C:9]2[O:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[CH:23]([C:25]1[CH:30]=[CH:29][C:28](B(O)O)=[CH:27][CH:26]=1)=[O:24].C([O-])([O-])=O.[Na+].[Na+]>C1C=CC(C#N)=CC=1.C1C=CC(C#N)=CC=1.Cl[Pd]Cl.CCO.O1CCCC1.C1(C)C=CC=CC=1>[O:16]([C:9]1[C:8]2[C:13](=[CH:14][CH:15]=[C:6]([C:28]3[CH:29]=[CH:30][C:25]([CH:23]=[O:24])=[CH:26][CH:27]=3)[CH:7]=2)[N:12]=[CH:11][N:10]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

9

Reactant 4

HCID 7843ButaneHCID 10340Sodium CarbonateHCID 5910734-Formylphenylboronic AcidHCID 113024646-Iodo4-phenoxyquinazoline

Product 1

HCID 111631824-(4-Phenoxy-quinazolin-6-yl)benzaldehydeYield 94%

Reagents, catalysts & solvents 4

HCID 498840Bis(benzonitrile)palladium chlorideCatalystHCID 702EthanolSolventHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of toluene (211 mL) in a 1.0 L round-bottom flask equipped with a reflux condenser was added 1,4-bis(diphenyl)phosphino)-butane (1.22 g, 2.87 mmol) and bis(benzonitrile)dichloro-palladium (1.1 g, 2.87 mmol). The resulting solution was stirred at room temperature for 30 minutes followed by the addition of THF (tetrahydrofuran) (255 mL) and EtOH (115 mL). To the resulting mixture was added 6-iodo-4-phenoxy-quinazoline 14 (5.0 g, 14.4 mmol), 4-formylphenylboronic acid (4.3 g, 28.7 mmol) and aqueous 1M Na2CO3 (29 mL). The mixture was heated at reflux under an atmosphere of N2 for 18 hours. The reaction mixture was filtered hot and the solvent removed under reduced pressure. The residue was taken up in CHCl3 and washed with water, brine, and dried (MgSO4). The solvent was removed under reduced pressure and the residue was purified using flash chromatography (silica gel, EtOAc/hexanes 4:6) to provide (4.42 g, 13.54 mmol) 4-(4-phenoxy-quinazolin-6-yl)benzaldehyde 15 in 94% yield. 1H NMR (CDCl3) δ 7.26 (m, 3H), 2.88 (m, 1H), 7.51 (M, 2H), 7.92 (d, 2H, J=8.4 Hz), 8.02 (d, 2H, J=8 Hz), 8.11 (d, 1H, J=8.8 Hz), 8.20 (dd, 1H, J=2.4 and 8.8 Hz), 8.63 (d, 1H, J=2.4 Hz), 8.79 (s, 1H); MS (Cl) m/e 326 (M++1, 100).

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux under an atmosphere of N2 for 18 hours
  3. filtrationThe reaction mixture was filtered hot
  4. customthe solvent removed under reduced pressure
  5. washwashed with water, brine
  6. dry with materialdried (MgSO4)
  7. customThe solvent was removed under reduced pressure
  8. customthe residue was purified

Sources & evidence

ORD record
ord-c29c52557c18459b824c8ea81472d7e2
Source dataset
uspto-grants-2005_03
Patent number
US06867201B2

Reaction notes

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