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Ethyl bromoacetate → (4-chloro-2-fluoro-9-trifluoromethyl-9H-fluoren-9-yloxy)-acetic acid ethyl ester

HRID 1798997
Notes
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Reaction equation

HRID 1798997 reaction equation
[Cl:1][C:2]1[C:14]2[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:7](=[O:15])[C:6]=2[CH:5]=[C:4]([F:16])[CH:3]=1.C(=O)([O-])[O-].[K+].[K+].C[Si](C)(C)[C:25]([F:28])([F:27])[F:26].[F-].[Cs+].Br[CH2:34][C:35]([O:37][CH2:38][CH3:39])=[O:36]>O.CN(C)C=O>[CH2:38]([O:37][C:35](=[O:36])[CH2:34][O:15][C:7]1([C:25]([F:28])([F:27])[F:26])[C:6]2[CH:5]=[C:4]([F:16])[CH:3]=[C:2]([Cl:1])[C:14]=2[C:13]2[C:8]1=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH3:39]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 5

HCID 7748Ethyl bromoacetateHCID 11430Potassium CarbonateHCID 25953Cesium fluorideHCID 552549(Trifluoromethyl)trimethylsilaneHCID 594925814-Chloro-2-fluoro-fluoren-9-one

Product 1

HCID 59492796(4-chloro-2-fluoro-9-trifluoromethyl-9H-fluoren-9-yloxy)-acetic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a mixture of dimethylformamide (1000 ml) and 4-chloro-2-fluoro-fluoren-9-one (204 g) was added potassium carbonate (36.4 g), and the mixture was stirred in a water bath. To this mixture was added dropwise trimethyl(trifluoromethyl)silane (156 ml) over 30 min, and the mixture was further stirred at room temperature for 30 min. To the reaction mixture was added cesium fluoride (173 g), ethyl bromoacetate (75 ml) was added dropwise over 20 min, and the mixture was stirred at room temperature. Water (1000 ml) was added to the reaction mixture, and the mixture was placed in a separatory funnel, and extracted with ethyl acetate (1000 ml). The organic layer was washed twice with brine (water:saturated brine=4:1, 1000 ml) and once with saturated brine (500 ml), dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure to give the title compound (360 g). The obtained residue was directly used for the next reaction without further purification.

Workup

  1. stirringthe mixture was further stirred at room temperature for 30 min
  2. additionwas added dropwise over 20 min
  3. stirringthe mixture was stirred at room temperature
  4. customthe mixture was placed in a separatory funnel
  5. extractionextracted with ethyl acetate (1000 ml)
  6. washThe organic layer was washed twice with brine (water:saturated brine=4:1, 1000 ml) and once with saturated brine (500 ml)
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationThe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-d46b871eabfd447181d4d7c538f19da7
Source dataset
uspto-grants-2013_01
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08343994B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes