4-Chloro-2-fluorophenol → 7-Benzyloxy-4-(4-chloro-2-fluorophenoxy)-6-methoxyquinazoline

HRID 279574

Reaction equation

HRID 279574 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([F:9])[CH:3]=1.Cl.[CH2:11]([O:18][C:19]1[CH:28]=[C:27]2[C:22]([C:23](Cl)=[N:24][CH:25]=[N:26]2)=[CH:21][C:20]=1[O:30][CH3:31])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>N1C=CC=CC=1>[CH2:11]([O:18][C:19]1[CH:28]=[C:27]2[C:22]([C:23]([O:8][C:5]3[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][C:4]=3[F:9])=[N:24][CH:25]=[N:26]2)=[CH:21][C:20]=1[O:30][CH3:31])[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1

Participants

4

Reactant 2

HCID 1819754-Chloro-2-fluorophenolHCID 220308367-(Benzyloxy)-4-chloro-6-methoxyquinazoline hydrochloride

Product 1

HCID 218748257-Benzyloxy-4-(4-chloro-2-fluorophenoxy)-6-methoxyquinazolineYield 77%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

4-Chloro-2-fluoro-phenol (264 mg, 1.8 mmol) was added to a solution of 7-benzyloxy-4-chloro-6-methoxyquinazoline hydrochloride (506 mg, 1.5 mmol), (prepared as described for the starting material in Example 1), in pyridine (8 ml) and the mixture heated at reflux for 45 minutes. The solvent was removed by evaporation and the residue partitioned between ethyl acetate and water. The organic layer was washed with 0.1M hydrochloric acid, water and brine, dried (MgSO4) and the solvent removed by evaporation. The solid residue was triturated with petroleum ether and the crude product collected by filtration and purified by flash chromatography eluting with methylene chloride/ether (9/1) to give 7-benzyloxy-4-(4-chloro-2-fluorophenoxy)-6-methoxyquinazoline (474 mg, 77%) as a cream solid.

Workup

  1. custom(prepared
  2. temperaturethe mixture heated
  3. temperatureat reflux for 45 minutes
  4. customThe solvent was removed by evaporation
  5. customthe residue partitioned between ethyl acetate and water
  6. washThe organic layer was washed with 0.1M hydrochloric acid, water and brine
  7. dry with materialdried (MgSO4)
  8. customthe solvent removed by evaporation
  9. customThe solid residue was triturated with petroleum ether
  10. filtrationthe crude product collected by filtration
  11. custompurified by flash chromatography
  12. washeluting with methylene chloride/ether (9/1)

Sources & evidence

ORD record
ord-8df83238fa9745758f57a2fcb0296b6a
Source dataset
uspto-grants-2002_03
Patent number
US06362336B1

Linked notes

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