4-(4-Chloro-2-fluorophenoxy)-6-methoxy-7-(2-(tert-butoxycarbonyl)vinyl)quinazoline → 7-(2-Carboxyvinyl)-4-(4-chloro-2-fluorophenoxy)-6-methoxyquinazoline
Reaction equation
[Cl:1][C:2]1[CH:29]=[CH:28][C:5]([O:6][C:7]2[C:16]3[C:11](=[CH:12][C:13]([CH:19]=[CH:20][C:21]([O:23]C(C)(C)C)=[O:22])=[C:14]([O:17][CH3:18])[CH:15]=3)[N:10]=[CH:9][N:8]=2)=[C:4]([F:30])[CH:3]=1>C(Cl)Cl.C(O)(C(F)(F)F)=O>[C:21]([CH:20]=[CH:19][C:13]1[CH:12]=[C:11]2[C:16]([C:7]([O:6][C:5]3[CH:28]=[CH:29][C:2]([Cl:1])=[CH:3][C:4]=3[F:30])=[N:8][CH:9]=[N:10]2)=[CH:15][C:14]=1[O:17][CH3:18])([OH:23])=[O:22]Participants
3
Procedure
A solution of 4-(4-chloro-2-fluorophenoxy)-6-methoxy-7-(2-(tert-butoxycarbonyl)vinyl)quinazoline (581 mg, 1.31 mmol) in a mixture of methylene chloride/TFA (2.5 ml/2.5 ml) was stirred at ambient temperature for 1.5 hours. After removal of the volatiles under vacuum, the residue was partitioned between ethyl acetate and water. The aqueous layer was adjusted to pH3 with 0.5M sodium hydroxide. The organic layer was separated and the aqueous layer was further extracted with ethyl acetate. The combined organic layers were washed with brine, dried (MgSO4) and evaporated to give 7-(2-carboxyvinyl)-4-(4-chloro-2-fluorophenoxy)-6-methoxyquinazoline (430 mg, 85%).
Workup
- customAfter removal of the volatiles under vacuum
- customthe residue was partitioned between ethyl acetate and water
- customThe organic layer was separated
- extractionthe aqueous layer was further extracted with ethyl acetate
- washThe combined organic layers were washed with brine
- dry with materialdried (MgSO4)
- customevaporated
Sources & evidence
- ORD record
- ord-c2ced24ea7c54a0784f61dd5b4f71b4e
- Source dataset
- uspto-grants-2013_07
- Patent number
- US08492560B2
Reaction notes
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