Dimethylformamide → tert-Butyl 4-(((4-(4-amino-3-fluorophenoxy)-6-cyano-7-quinolyl)oxy)methyl)-1-piperidinecarboxylate

HRID 1433706Notes

Reaction equation

HRID 1433706 reaction equation
[NH2:1][C:2]1[CH:21]=[CH:20][C:5]([O:6][C:7]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([C:17]#[N:18])[CH:15]=3)[N:10](O)[CH2:9][CH:8]=2)=[CH:4][C:3]=1[F:22].Br[CH2:24][CH:25]1[CH2:30][CH2:29][N:28]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:27][CH2:26]1.C(=O)([O-])[O-:39].[K+].[K+].CN(C)C=O>C(OCC)(=O)C.CCCCCC.O>[NH2:1][C:2]1[CH:21]=[CH:20][C:5]([O:6][C:7]2[C:16]3[C:11](=[CH:12][C:13]([O:39][CH2:24][CH:25]4[CH2:30][CH2:29][N:28]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:27][CH2:26]4)=[C:14]([C:17]#[N:18])[CH:15]=3)[N:10]=[CH:9][CH:8]=2)=[CH:4][C:3]=1[F:22]

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 15512811tert-Butyl 4-(bromomethyl)piperidine-1-carboxylateHCID 86608918HCID 86608918, compound

Product 1

HCID 22936777tert-Butyl 4-(((4-(4-amino-3-fluorophenoxy)-6-cyano-7-quinolyl)oxy)methyl)-1-piperidinecarboxylateYield 51.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent3×

Procedure

4-(4-Amino-3-fluorophenoxy)-1-hydroxy-6-quinoline carbonitrile (500 mg), tert-butyl 4-(bromomethyl)-1-piperidinecarboxylate (550 mg), potassium carbonate (700 mg) and dimethylformamide (5 ml) were stirred together at 60° C. for 2 hours. Water and ethyl acetate were added for extraction, and the extract was dried over magnesium sulfate. The drying agent was filtered out, and silica gel was added to the filtrate which was then distilled off under reduced pressure for adsorption. The reaction solution-adsorbed silica gel was subjected to column chromatography (hexane:ethyl acetate=1:1, followed by 1:2, 1:3, ethyl acetate) in a dry column packed with silica gel, to obtain 423 mg of a brown oil.

Workup

  1. dry with materialthe extract was dried over magnesium sulfate
  2. filtrationThe drying agent was filtered out
  3. additionsilica gel was added to the filtrate which
  4. distillationwas then distilled off under reduced pressure for adsorption
  5. customThe reaction solution-adsorbed silica gel

Sources & evidence

ORD record
ord-3926729abf1549869328a5f539f18f1b
Source dataset
uspto-grants-2009_11
Patent number
US07612092B2

Reaction notes

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