Cesium carbonate → Methyl 3-cyclopropyl-3-(3-((6-(2,2-dimethylpropyl)-5-(2-fluoro-5-methoxyphenyl)pyridin-2-yl)methoxy)-4-fluorophenyl)propanoate

HRID 709669Notes

Reaction equation

HRID 709669 reaction equation
Cl[CH2:2][C:3]1[N:8]=[C:7]([CH2:9][C:10]([CH3:13])([CH3:12])[CH3:11])[C:6]([C:14]2[CH:19]=[C:18]([O:20][CH3:21])[CH:17]=[CH:16][C:15]=2[F:22])=[CH:5][CH:4]=1.[CH:23]1([CH:26]([C:32]2[CH:37]=[CH:36][C:35]([F:38])=[C:34]([OH:39])[CH:33]=2)[CH2:27][C:28]([O:30][CH3:31])=[O:29])[CH2:25][CH2:24]1.C(=O)([O-])[O-].[Cs+].[Cs+]>C(#N)C>[CH:23]1([CH:26]([C:32]2[CH:37]=[CH:36][C:35]([F:38])=[C:34]([O:39][CH2:2][C:3]3[CH:4]=[CH:5][C:6]([C:14]4[CH:19]=[C:18]([O:20][CH3:21])[CH:17]=[CH:16][C:15]=4[F:22])=[C:7]([CH2:9][C:10]([CH3:13])([CH3:12])[CH3:11])[N:8]=3)[CH:33]=2)[CH2:27][C:28]([O:30][CH3:31])=[O:29])[CH2:24][CH2:25]1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 1177599996-(Chloromethyl)-2-(2,2-dimethylpropyl)-3-(2-fluoro-5-methoxyphenyl)pyridineHCID 117760257Methyl 3-cyclopropyl-3-(4-fluoro-3-hydroxyphenyl)propanoate

Product 1

HCID 117760040Methyl 3-cyclopropyl-3-(3-((6-(2,2-dimethylpropyl)-5-(2-fluoro-5-methoxyphenyl)pyridin-2-yl)methoxy)-4-fluorophenyl)propanoateYield 82.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 6-(chloromethyl)-2-(2,2-dimethylpropyl)-3-(2-fluoro-5-methoxyphenyl)pyridine (320 mg) in acetonitrile (30 mL) were added methyl 3-cyclopropyl-3-(4-fluoro-3-hydroxyphenyl)propanoate (220 mg) and cesium carbonate (550 mg), and the mixture was heated under reflux for 15 hr. The reaction mixture was concentrated, and water was added to the residue. The mixture was extracted with ethyl acetate, and the extract was washed with saturated brine. The organic layer was dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (400 mg) as a yellow oil.

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 15 hr
  3. concentrationThe reaction mixture was concentrated
  4. additionwater was added to the residue
  5. extractionThe mixture was extracted with ethyl acetate
  6. washthe extract was washed with saturated brine
  7. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  8. customthe solvent was evaporated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexane)

Sources & evidence

ORD record
ord-00dd3c95229c41b998f5e274eb08e94a
Source dataset
uspto-grants-2015_11
Patent number
US09181186B2

Reaction notes

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