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

HRID 991465Notes

Reaction equation

HRID 991465 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 ) δ7.26 (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-d8ea958a16174db6b8c475025e4d3f2f
Source dataset
uspto-grants-2002_10
Patent number
US06465449B1

Reaction notes

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