Water → 7-Benzyloxy-6-methoxy-4-phenoxyquinazoline

HRID 453982Notes

Reaction equation

HRID 453982 reaction equation
[C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].[CH2:10]([O:17][C:18]1[CH:27]=[C:26]2[C:21]([C:22](Cl)=[N:23][CH:24]=[N:25]2)=[CH:20][C:19]=1[O:29][CH3:30])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.O>CN1C(=O)CCC1>[CH2:10]([O:17][C:18]1[CH:27]=[C:26]2[C:21]([C:22]([O:7][C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)=[N:23][CH:24]=[N:25]2)=[CH:20][C:19]=1[O:29][CH3:30])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

6

Reactant 4

HCID 962WaterHCID 996PhenolHCID 24758Sodium hydrideHCID 106619987-(Benzyloxy)-4-chloro-6-methoxyquinazoline

Product 1

HCID 218748147-Benzyloxy-6-methoxy-4-phenoxyquinazolineYield 83%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent2×

Procedure

Phenol (29.05 g, 309 mmol) was dissolved in NMP (210 ml), sodium hydride (11.025 g, 60% dispersion in mineral oil) was added in portions with cooling and the mixture was stirred for 3 hours. The viscous suspension was diluted with NMP (180 ml) and stirred overnight. The solution of 7-benzyloxy-4-chloro-6-methoxyquinazoline was added and the suspension stirred at 100° C. for 2.5 hours. The suspension was allowed to cool to ambient temperature and poured into water (1.5 l) with vigorous stirring. The precipitate was collected by filtration, washed with water and dried under vacuum. The residue was dissolved in dichloromethane, washed with brine and filtered through phase separating paper. The filtrate was evaporated under vacuum then triturated with ether to give 7-benzyloxy-6-methoxy-4-phenoxyquinazoline (87.8 g, 83%) as a pale cream solid.

Workup

  1. temperaturewith cooling
  2. stirringstirred overnight
  3. stirringthe suspension stirred at 100° C. for 2.5 hours
  4. filtrationThe precipitate was collected by filtration
  5. washwashed with water
  6. customdried under vacuum
  7. dissolutionThe residue was dissolved in dichloromethane
  8. washwashed with brine
  9. filtrationfiltered through phase
  10. customseparating paper
  11. customThe filtrate was evaporated under vacuum
  12. customthen triturated with ether

Sources & evidence

ORD record
ord-14d0cc1780fa412d95c08bcd648e186f
Source dataset
uspto-grants-2013_07
Patent number
US08492560B2

Reaction notes

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