Water → 4-(4-Amino-3-fluoro-phenoxy)-7-[(2R)-oxiran-2-yl]methoxyquinoline-6-carbonitrile
Reaction equation
CN(C)C=O.C(=O)([O-])[O-].[K+].[K+].[NH2:12][C:13]1[CH:32]=[CH:31][C:16]([O:17][C:18]2[C:27]3[C:22](=[CH:23][C:24]([OH:30])=[C:25]([C:28]#[N:29])[CH:26]=3)[N:21]=[CH:20][CH:19]=2)=[CH:15][C:14]=1[F:33].O.[C:35]([O:38][CH2:39][CH3:40])(=O)C>>[NH2:12][C:13]1[CH:32]=[CH:31][C:16]([O:17][C:18]2[C:27]3[C:22](=[CH:23][C:24]([O:30][CH2:40][C@H:39]4[CH2:35][O:38]4)=[C:25]([C:28]#[N:29])[CH:26]=3)[N:21]=[CH:20][CH:19]=2)=[CH:15][C:14]=1[F:33]Participants
6
Conditions
- Temperature
- 50 °C
Procedure
After adding dimethylformamide (8 ml), p-toluenesulfonic acid (2R)-glycidyl ester (1000 mg) and potassium carbonate (940 mg) to 4-(4-amino-3-fluorophenoxy)-6-cyano-7-hydroxyquinoline (1000 mg), the mixture was heated at 50° C. for 4 hours. Water was added to the reaction solution, extraction was performed with ethyl acetate, and then the organic layer was washed with water and saturated saline in that order and dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained crude product was purified by silica gel column chromatography (ethyl acetate) to obtain the title compound (659 mg) as light yellow crystals.
Workup
- washthe organic layer was washed with water and saturated saline in that order
- dry with materialdried over anhydrous sodium sulfate
- distillationthe solvent was distilled off under reduced pressure
- customThe obtained crude product
- customwas purified by silica gel column chromatography (ethyl acetate)
Sources & evidence
- ORD record
- ord-d0241d236eee45dfa63924a8bc2863d9
- Source dataset
- uspto-grants-2013_02
- Patent number
- US08372981B2
Reaction notes
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