Ethyl Acrylate → (E)-(3,7-Difluoro-6H-dibenzo[b,e]oxepin-11-ylidene)-acetic acid ethyl ester

HRID 1670599Notes

Reaction equation

HRID 1670599 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[C:16]([F:17])=[CH:15][CH:14]=[CH:13][C:12]=1Br.[C:19]([O:23][CH2:24][CH3:25])(=[O:22])[CH:20]=[CH2:21].C([O-])(=O)C.[Na+]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.CN1CCCC1=O.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH2:24]([O:23][C:19](=[O:22])/[CH:20]=[C:21]1/[C:2]2[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=2[O:9][CH2:10][C:11]2[C:16]([F:17])=[CH:15][CH:14]=[CH:13][C:12]/1=2)[CH3:25]

Participants

7

Reactant 3

HCID 8821Ethyl AcrylateHCID 517045Sodium AcetateHCID 673347191-Bromo-2-(2-bromo-6-fluoro-benzyloxy)-4-fluoro-benzene

Product 1

HCID 67335842(E)-(3,7-Difluoro-6H-dibenzo[b,e]oxepin-11-ylidene)-acetic acid ethyl esterYield 68.2%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
120 °C

Procedure

Degas a mixture of 1-bromo-2-(2-bromo-6-fluoro-benzyloxy)-4-fluoro-benzene (886 mmol, 335 g), ethyl acrylate (931 mmol, 101 mL, 1.05 eq), Pd(OAc)2 (22.2 mmol, 4.97 g), tetrabutylammonium bromide (886 mmol, 286 g), and sodium acetate (4.40 mol, 363.5 g) in N-methylpyrrolidinone (3.3 L) by evacuating and back-filling with nitrogen five times. Heat the mixture to 120° C. for 2 h. Cool to 35° C. and add water (5.5 L) over 40 min. Filter the precipitate, rinse with water (2×500 mL) and air dry for 30 min. Reslurry the in isopropanol (1 L) for 2 h and cool on ice for one hour. Collect the dark gray solid by filtration, rinse with cold isopropanol (5×100 mL) and dry at 50° C. in vacuo to obtain the title compound (191 g, 68%).

Workup

  1. customDegas
  2. customby evacuating and back-filling with nitrogen five times
  3. temperatureCool to 35° C.
  4. additionadd water (5.5 L) over 40 min
  5. filtrationFilter the precipitate
  6. washrinse with water (2×500 mL) and air
  7. customdry for 30 min
  8. customfor 2 h
  9. temperaturecool on ice for one hour
  10. customCollect the dark gray solid
  11. filtrationby filtration
  12. washrinse with cold isopropanol (5×100 mL)
  13. customdry at 50° C. in vacuo

Sources & evidence

ORD record
ord-329930cec3074d04ac81822d65f329d1
Source dataset
uspto-grants-2011_08
Patent number
US07994164B2

Reaction notes

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