Dimethylformamide → 4-(4-Amino-3-fluoro-phenoxy)-7-[(2R)-oxiran-2-yl]methoxyquinoline-6-carbonitrile

HRID 1010343Notes

Reaction equation

CN(C)C=O.CC1C=CC(S(O[CH2:17][C@@H:18]2[O:20][CH2:19]2)(=O)=O)=CC=1.C(=O)([O-])[O-].[K+].[K+].[NH2:27][C:28]1[CH:47]=[CH:46][C:31]([O:32][C:33]2[C:42]3[C:37](=[CH:38][C:39]([OH:45])=[C:40]([C:43]#[N:44])[CH:41]=3)[N:36]=[CH:35][CH:34]=2)=[CH:30][C:29]=1[F:48]>C(OCC)(=O)C.O>[NH2:27][C:28]1[CH:47]=[CH:46][C:31]([O:32][C:33]2[C:42]3[C:37](=[CH:38][C:39]([O:45][CH2:17][C@H:18]4[CH2:19][O:20]4)=[C:40]([C:43]#[N:44])[CH:41]=3)[N:36]=[CH:35][CH:34]=2)=[CH:30][C:29]=1[F:48]

Participants

Conditions

Temperature: 50 °C

Procedure

After adding dimethylformamide (8 ml), (2R)-(−)-glycidyl p-toluenesulfonate (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 brine 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 brine 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-79f09b21393f46b6b8fb8a6e35495b5a
Source dataset: uspto-grants-2011_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07973160B2

Reaction notes

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