Sodium Acetate → (E)-(3-Fluoro-6H-dibenzo[b,e]oxepin-11-ylidene)-acetic acid ethyl ester

HRID 244342Notes

Reaction equation

HRID 244342 reaction equation
[CH2:1]([O:3][C:4](=[O:23])[CH:5]=[CH:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[CH2:13][O:14][C:15]1[CH:20]=[C:19]([F:21])[CH:18]=[CH:17][C:16]=1Br)[CH3:2].C([O-])(=O)C.[Na+]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.CN1CCCC1=O.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:1]([O:3][C:4](=[O:23])/[CH:5]=[C:6]1/[C:16]2[CH:17]=[CH:18][C:19]([F:21])=[CH:20][C:15]=2[O:14][CH2:13][C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]/1=2)[CH3:2]

Participants

7

Reactant 2

HCID 517045Sodium AcetateHCID 671334433-[2-(2-Bromo-5-fluoro-phenoxymethyl)-phenyl]-acrylic acid ethyl ester

Product 1

HCID 67333776(E)-(3-Fluoro-6H-dibenzo[b,e]oxepin-11-ylidene)-acetic acid ethyl esterYield 87%

Reagents, catalysts & solvents 4

HCID 74236Tetrabutylammonium BromideCatalystHCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

Heat a mixture of 3-[2-(2-bromo-5-fluoro-phenoxymethyl)-phenyl]-acrylic acid ethyl ester (94 g, 0.25 mol), sodium acetate (30 g, 0.37 mol), tetra-n-butylammonium bromide (81 g, 0.25 mol), and palladium (II) acetate (1.7 g, 7 mmol, 3 mol %) in N-methylpyrrolidinone (850 mL) at 100-110° C. for 6 h. Cool to room temperature, dilute with water (1 L), filter through diatomaceous earth, and wash with ethyl acetate (2 L). Transfer the filtrate to a separatory funnel, add water (500 mL) and separate the layers. Wash the organic layer with water (2×1.5 L), dry over anhydrous sodium sulfate, filter through a silica pad, wash with ethyl acetate (1.5 L) and concentrate to dryness. To the residual solid add hexanes (1 L), refrigerate for 2 h, filter, rinse with hexanes (500 mL), and dry at 50° C./20 mm Hg to obtain the title compound (64.3 g, 87%). LC-MS m/z 299.0 [M+H]+.

Workup

  1. temperatureHeat
  2. filtrationfilter through diatomaceous earth
  3. washwash with ethyl acetate (2 L)
  4. additionTransfer the filtrate to a separatory funnel, add water (500 mL)
  5. customseparate the layers
  6. washWash the organic layer with water (2×1.5 L)
  7. dry with materialdry over anhydrous sodium sulfate
  8. filtrationfilter through a silica pad
  9. washwash with ethyl acetate (1.5 L)
  10. concentrationconcentrate to dryness
  11. additionTo the residual solid add hexanes (1 L)
  12. filtrationfilter
  13. washrinse with hexanes (500 mL)
  14. customdry at 50° C./20 mm Hg

Sources & evidence

ORD record
ord-19a5d2e15abd4cee88bfdefc244aece0
Source dataset
uspto-grants-2014_02
Patent number
US08658638B2

Reaction notes

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