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Pyridine → 4-(4-Chloro-2-fluorophenoxy)-6-methoxy-7-(trifluoromethylsulphonyloxy)quinazoline

HRID 1791605
Notes
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Reaction equation

HRID 1791605 reaction equation
FC(F)(F)S([O:6][S:7]([C:10]([F:13])([F:12])[F:11])(=[O:9])=[O:8])(=O)=O.[Cl:16][C:17]1[CH:36]=[CH:35][C:20]([O:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](O)=[C:29]([O:32][CH3:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)=[C:19]([F:37])[CH:18]=1.N1C=CC=CC=1>C(Cl)Cl>[Cl:16][C:17]1[CH:36]=[CH:35][C:20]([O:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:6][S:7]([C:10]([F:11])([F:12])[F:13])(=[O:8])=[O:9])=[C:29]([O:32][CH3:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)=[C:19]([F:37])[CH:18]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 3

HCID 1049PyridineHCID 67749Trifluoromethanesulfonic anhydrideHCID 1356162044-(4-Chloro-2-fluorophenoxy)-7-hydroxy-6-methoxyquinazoline

Product 1

HCID 220308424-(4-Chloro-2-fluorophenoxy)-6-methoxy-7-(trifluoromethylsulphonyloxy)quinazolineYield 88.5%

Reagents, catalysts & solvents 1

HCID 6344
Dichloromethane
Solvent

Conditions

Temperature
5 °C

Procedure

Trifluoromethanesulphonic anhydride (338 mg, 1.2 mmol) was added to a suspension of 4-(4-chloro-2-fluorophenoxy)-7-hydroxy-6-methoxyquinazoline (320 mg, I mmol), (prepared as described for the starting material in Example 5), in methylene chloride (2 ml) containing pyridine (2 ml) cooled at 5° C. When the addition was complete, the mixture was left to warm to ambient temperature and stirred for 1 hour. After removal of the volatiles by evaporation, the residue was partitioned between ethyl acetate/ether and water. The organic layer was separated, washed with 0.5M hydrochloric acid, followed by water, brine, dried (MgSO4) and evaporated to give 4-(4-chloro-2-fluorophenoxy)-6-methoxy-7-(trifluoromethylsulphonyloxy)quinazoline (400 mg, 88%).

Workup

  1. custom(prepared
  2. additionWhen the addition
  3. waitthe mixture was left
  4. temperatureto warm to ambient temperature
  5. customAfter removal of the volatiles
  6. customby evaporation
  7. customthe residue was partitioned between ethyl acetate/ether and water
  8. customThe organic layer was separated
  9. washwashed with 0.5M hydrochloric acid
  10. dry with materialdried (MgSO4)
  11. customevaporated

Sources & evidence

ORD record
ord-7541a0616eea4860b1a30bd7bd123fbd
Source dataset
uspto-grants-2006_07
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07074800B1

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes