Pyridine → tert-Butyl 4-(((6-cyano-4-(3-fluoro-4-((phenoxycarbonyl)amino)phenoxy)-7-quinolyl)oxy)methyl)-1-piperidinecarboxylate

HRID 1010436Notes

Reaction equation

HRID 1010436 reaction equation
[NH2:1][C:2]1[CH:35]=[CH:34][C:5]([O:6][C:7]2[C:16]3[C:11](=[CH:12][C:13]([O:19][CH2:20][CH:21]4[CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:23][CH2:22]4)=[C:14]([C:17]#[N:18])[CH:15]=3)[N:10]=[CH:9][CH:8]=2)=[CH:4][C:3]=1[F:36].N1C=CC=CC=1.Cl[C:44]([O:46][C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1)=[O:45]>O1CCCC1>[C:17]([C:14]1[CH:15]=[C:16]2[C:11](=[CH:12][C:13]=1[O:19][CH2:20][CH:21]1[CH2:22][CH2:23][N:24]([C:27]([O:29][C:30]([CH3:32])([CH3:31])[CH3:33])=[O:28])[CH2:25][CH2:26]1)[N:10]=[CH:9][CH:8]=[C:7]2[O:6][C:5]1[CH:34]=[CH:35][C:2]([NH:1][C:44]([O:46][C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=2)=[O:45])=[C:3]([F:36])[CH:4]=1)#[N:18]

Participants

5

Reactant 3

HCID 1049PyridineHCID 15891Phenyl chloroformateHCID 22936777tert-Butyl 4-(((4-(4-amino-3-fluorophenoxy)-6-cyano-7-quinolyl)oxy)methyl)-1-piperidinecarboxylate

Product 1

HCID 22936279tert-Butyl 4-(((6-cyano-4-(3-fluoro-4-((phenoxycarbonyl)amino)phenoxy)-7-quinolyl)oxy)methyl)-1-piperidinecarboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

tert-Butyl 4-(((4-(4-amino-3-fluorophenoxy)-6-cyano-7-quinolyl)oxy)methyl)-1-piperidinecarboxylate (523 mg), pyridine (0.17 ml) and tetrahydrofuran (10 ml) were stirred while cooling on ice, and then phenyl chloroformate was added dropwise. Immediately after completion of the dropwise addition, the cooling bath was removed and the mixture was returned to room temperature. After 15 minutes of stirring, water and ethyl acetate were added for extraction. Silica gel was added to the extract and the solvent was distilled off under reduced pressure for adsorption. The reaction solution-adsorbed silica gel was purified by column chromatography (hexane:ethyl acetate=1:1, followed by 1:2, ethyl acetate) in a dry column packed with silica gel, to obtain 490 mg of a yellow powder.

Workup

  1. temperaturewhile cooling on ice
  2. additionImmediately after completion of the dropwise addition
  3. customthe cooling bath was removed
  4. customwas returned to room temperature
  5. additionwater and ethyl acetate were added for extraction
  6. additionSilica gel was added to the
  7. extractionextract
  8. distillationthe solvent was distilled off under reduced pressure for adsorption
  9. customThe reaction solution-adsorbed silica gel
  10. customwas purified by column chromatography (hexane:ethyl acetate=1:1, followed by 1:2, ethyl acetate) in a dry column

Sources & evidence

ORD record
ord-d5b9c46532b841d8ae5c360c49975153
Source dataset
uspto-grants-2011_07
Patent number
US07973160B2

Reaction notes

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