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

HRID 244344Notes

Reaction equation

HRID 244344 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[O:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1I.C([O-])(=O)C.[Na+].[C:23]([O:27][CH2:28][CH3:29])(=[O:26])[CH:24]=[CH2:25]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.CN1CCCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:28]([O:27][C:23](=[O:26])/[CH:24]=[C:25]1/[C:2]2[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=2[O:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]/1=2)[CH3:29]

Participants

7

Reactant 3

HCID 8821Ethyl AcrylateHCID 517045Sodium AcetateHCID 585644251-Bromo-4-fluoro-2-(2-iodo-benzyloxy)-benzene

Product 1

HCID 67333776(E)-(3-Fluoro-6H-dibenzo[b,e]oxepin-11-ylidene)-acetic acid ethyl esterYield 61%

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 167845palladium(II) acetateCatalystHCID 84541-MethylpyrrolidineSolvent2×

Conditions

Temperature
145 °C

Procedure

Heat 1-bromo-4-fluoro-2-(2-iodo-benzyloxy)-benzene (50 g, 0.123 mol), sodium acetate (30.2 g, 0.369 mol), tetrabutylammonium bromide (39.6 g, 0.123 mol), and palladium acetate (1 g) in N-methylpyrrolidine (250 mL) to 60° C. Add ethyl acrylate (12.91 g, 0.129 mol) in N-methylpyrrolidine (50 mL) dropwise over 20 min. After the addition is complete, heat the reaction mixture to 145° C. for 3 h. Cool the reaction mixture to room temperature, filter through diatomaceous earth, and wash the solids with methyl t-butyl ether (2×150 mL). Dilute the filtrate with methyl t-butyl ether (0.5 L) and wash with water (0.5 L). Separate the organic layer and extract the aqueous layer with methyl t-butyl ether (2×300 mL). Wash the combined organic layers with water (2×200 mL). Dry the organic portion over magnesium sulfate, treat with charcoal, filter, wash the solids with methyl t-butyl ether (100 mL) and concentrate. Slurry the residue in isopropanol (20 mL) in a Buchi flask at 55° C. without vacuum. Add heptanes (100 mL) with stirring. Place the dark suspension in a cold room overnight. Filter the solids, rinse with cold heptane/isopropanol (9:1, 2×100 mL), then heptane (50 mL) and dry to a constant weight in a vacuum oven at 35° C. to obtain the title compound as a tan powder (22.25 g, 61%).

Workup

  1. additionAfter the addition
  2. temperatureCool the reaction mixture to room temperature
  3. filtrationfilter through diatomaceous earth
  4. washwash the solids with methyl t-butyl ether (2×150 mL)
  5. additionDilute the filtrate with methyl t-butyl ether (0.5 L)
  6. washwash with water (0.5 L)
  7. customSeparate the organic layer
  8. extractionextract the aqueous layer with methyl t-butyl ether (2×300 mL)
  9. washWash the combined organic layers with water (2×200 mL)
  10. dry with materialDry the organic portion over magnesium sulfate
  11. additiontreat with charcoal
  12. filtrationfilter
  13. washwash the solids with methyl t-butyl ether (100 mL)
  14. concentrationconcentrate
  15. customat 55° C.
  16. customin a cold room overnight
  17. filtrationFilter the solids
  18. washrinse with cold heptane/isopropanol (9:1, 2×100 mL)
  19. dry with materialheptane (50 mL) and dry to a constant weight in a vacuum oven at 35° C.

Sources & evidence

ORD record
ord-60a8adf0121248169a0594352381d0ae
Source dataset
uspto-grants-2014_02
Patent number
US08658638B2

Reaction notes

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