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

HRID 1384588Notes

Reaction equation

HRID 1384588 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. m.p. 179-180° C. 1H NMR Spectrum: (DMSOd6) 3.99(s, 3H); 5.36(s, 3H); 7.35-7.5(m, 4H); 7.55-7.65(m, 5H); 7.72(d, 1H); 8.6(s, 1H) MS-ESI: 411 [MH]+

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-f992f0e3491d414683cf4db93bba3c03
Source dataset
uspto-grants-2001_07
Patent number
US06258951B1

Reaction notes

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