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Ethyl Acetate → 2-Chloro-8-[6-(4-trifluoromethyl-phenyl)-pyrimidin-4-yloxy]-quinoline

HRID 2055926
Notes
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Reaction equation

HRID 2055926 reaction equation
Cl[C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][CH:9]=2)[N:5]=[CH:4][N:3]=1.[Cl:18][C:19]1[CH:28]=[CH:27][C:26]2[C:21](=[C:22]([OH:29])[CH:23]=[CH:24][CH:25]=2)[N:20]=1.C(=O)([O-])[O-].[K+].[K+].CCOC(C)=O>CN(C=O)C.[Cl-].[Na+].O>[Cl:18][C:19]1[CH:28]=[CH:27][C:26]2[C:21](=[C:22]([O:29][C:2]3[CH:7]=[C:6]([C:8]4[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][CH:9]=4)[N:5]=[CH:4][N:3]=3)[CH:23]=[CH:24][CH:25]=2)[N:20]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 2748782-Chloroquinolin-8-olHCID 167478374-Chloro-6-(4-(trifluoromethyl)phenyl)pyrimidine

Product 1

HCID 100240132-Chloro-8-[6-(4-trifluoromethyl-phenyl)-pyrimidin-4-yloxy]-quinoline

Reagents, catalysts & solvents 2

HCID 6228
Dimethylformamide
Solvent
HCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 4-chloro-6-(4-trifluoromethyl-phenyl)-pyrimidine, (Example 2(a), Method A), (259 mg, 1 mmol) and 2-chloro-quinolin-8-ol (Example 2(a), Method B), (180 mg, 1 mmol) in 2 mL of DMF was added potassium carbonate (276 mg, 2 mmol). The reaction was stirred in a 90° C. oil bath for 2 h. EtOAc and brine were added, and the aqueous layer was extracted with EtOAc. The combined EtOAc layers were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuum. Purification by flash chromatography by silica gel chromatography 1:4 of EtOAc/hexanes as eluent gave the title compound as a white solid. MS (ESI, pos. ion) m/z: 402 (M+1). Mp: 171.5-173.0° C. Anal. Calcd for C20H11ClF3N3O: C, 59.79; H, 2.76; N, 10.46. Found: C, 60.01; H, 2.80; N, 10.50.

Workup

  1. extractionthe aqueous layer was extracted with EtOAc
  2. washThe combined EtOAc layers were washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuum
  6. customPurification by flash chromatography by silica gel chromatography 1:4 of EtOAc/hexanes as eluent

Sources & evidence

ORD record
ord-880cbd6cabca4ad49cf4765e711c89e4
Source dataset
uspto-grants-2008_02
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07332511B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes