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Cesium carbonate → (6-Trifluoromethyl-pyridin-2-yl)-acetic acid ethyl ester

HRID 467983
Notes
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Reaction equation

HRID 467983 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].[C:7](P(C(C)(C)C)C(C)(C)C)(C)(C)[CH3:8].Br[C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:29])[F:28])[N:22]=1.C([C:33](CC)([C:37]([O-:39])=[O:38])C([O-])=O)C.[Cl-].[NH4+]>COCCOC.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:7]([O:39][C:37](=[O:38])[CH2:33][C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:29])[F:28])[N:22]=1)[CH3:8]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 5

HCID 10796Cesium carbonateHCID 25517Ammonium ChlorideHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 27829022-Bromo-6-(trifluoromethyl)pyridineHCID 69515632,2-Diethylpropanedioate

Product 1

HCID 58216744(6-Trifluoromethyl-pyridin-2-yl)-acetic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of caesium carbonate (1.87 g, 5.75 mmol) and tri-t-butylphosphine (107 μL, 0.44 mmol) in dry 1,2 dimethoxyethane (10 mL) was treated with tris-(dibenzylideneacetone)di-palladium (81 mg, 0.09 mmol), 2-Bromo-6-(trifluoromethyl)pyridine (1 g, 4.42 mmol) and diethylmalonate (0.8 mL, 5.3 mmol) under nitrogen atmosphere. The mixture was heated to 150° C. for 30 min in a microwave oven. After cooling to 20° C. the mixture was treated with a saturated solution of ammonium chloride (120 mL) and extracted with ethyl ether (3×80 mL). The organic phase was dried and evaporated to give a crude oil that was purified by flash chromatography eluting with n-hexane/ethyl ether 6/1.

Workup

  1. temperatureAfter cooling to 20° C. the mixture
  2. extractionextracted with ethyl ether (3×80 mL)
  3. customThe organic phase was dried
  4. customevaporated
  5. customto give a crude oil that
  6. customwas purified by flash chromatography
  7. washeluting with n-hexane/ethyl ether 6/1

Sources & evidence

ORD record
ord-324094b410cd4a10b7af947ebfe95bd2
Source dataset
uspto-grants-2014_01
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08623901B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes