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

HRID 453992Notes

Reaction equation

HRID 453992 reaction equation
[CH2:1]([O:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13](Cl)=[N:14][CH:15]=[N:16]2)=[CH:11][C:10]=1[O:20][CH3:21])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[Cl:28][C:29]1[CH:34]=[CH:33][C:32]([OH:35])=[C:31]([F:36])[CH:30]=1.O>CN(C=O)C>[CH2:1]([O:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13]([O:35][C:32]3[CH:33]=[CH:34][C:29]([Cl:28])=[CH:30][C:31]=3[F:36])=[N:14][CH:15]=[N:16]2)=[CH:11][C:10]=1[O:20][CH3:21])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 1819754-Chloro-2-fluorophenolHCID 106619987-(Benzyloxy)-4-chloro-6-methoxyquinazoline

Product 1

HCID 218748257-Benzyloxy-4-(4-chloro-2-fluorophenoxy)-6-methoxyquinazolineYield 76%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of the crude 7-benzyloxy-4-chloro-6-methoxyquinazoline, potassium carbonate (50 g, 362 mmol) and 4-chloro-2-fluorophenol (8.8 ml, 83 mmol) in DMF (500 ml) was stirred at 100° C. for 5 hours then allowed to cool to ambient temperature overnight. The reaction mixture was poured into water (2 l) and was stirred at ambient temperature for a few minutes. The crude solid was collected by filtration washing with water. The resultant solid was dissolved in dichloromethane and filtered through diatomaceous earth. The filtrate was treated with decolourising charcoal, boiled for a few minutes then filtered through diatomaceous earth. The filtrate was filtered through phase separating paper and then evaporated under vacuum to give a solid residue which was triturated with ether, filtered and dried to give 7-benzyloxy-4-(4-chloro-2-fluorophenoxy)-6-methoxyquinazoline (23.2 g, 76%).

Workup

  1. temperatureto cool to ambient temperature overnight
  2. stirringwas stirred at ambient temperature for a few minutes
  3. filtrationThe crude solid was collected by filtration
  4. washwashing with water
  5. dissolutionThe resultant solid was dissolved in dichloromethane
  6. filtrationfiltered through diatomaceous earth
  7. additionThe filtrate was treated with decolourising charcoal
  8. waitboiled for a few minutes
  9. filtrationthen filtered through diatomaceous earth
  10. filtrationThe filtrate was filtered through phase
  11. customseparating paper
  12. customevaporated under vacuum
  13. customto give a solid residue which
  14. customwas triturated with ether
  15. filtrationfiltered
  16. customdried

Sources & evidence

ORD record
ord-a2a84fea286e4fc284e1ddb7fd7a7f20
Source dataset
uspto-grants-2013_07
Patent number
US08492560B2

Reaction notes

Loading…