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

HRID 454164Notes

Reaction equation

HRID 454164 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) 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 HCl, 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. temperaturethe mixture heated
  2. temperatureat reflux for 45 minutes
  3. customThe solvent was removed by evaporation
  4. customthe residue partitioned between ethyl acetate and water
  5. washThe organic layer was washed with 0.1M HCl, water and brine
  6. dry with materialdried (MgSO4)
  7. customthe solvent removed by evaporation
  8. customThe solid residue was triturated with petroleum ether
  9. filtrationthe crude product collected by filtration
  10. custompurified by flash chromatography
  11. washeluting with methylene chloride/ether (9/1)

Sources & evidence

ORD record
ord-e9799813354d4156bebf462bdad6bc16
Source dataset
uspto-grants-2013_07
Patent number
US08492560B2

Reaction notes

Loading…