Water → 3-[2-(2-Bromo-5-fluoro-phenoxymethyl)-phenyl]-acrylic acid ethyl ester

HRID 1670592Notes

Reaction equation

HRID 1670592 reaction equation
[Br:1][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].O>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.CN1CCCC1=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(OCC)(=O)C.C(OC)(C)(C)C>[CH2:28]([O:27][C:23](=[O:26])[CH:24]=[CH:25][C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=1[CH2:10][O:9][C:3]1[CH:4]=[C:5]([F:8])[CH:6]=[CH:7][C:2]=1[Br:1])[CH3:29]

Participants

10

Reactant 4

HCID 962WaterHCID 8821Ethyl AcrylateHCID 517045Sodium AcetateHCID 58564425HCID 58564425, compound

Product 1

HCID 671334433-[2-(2-Bromo-5-fluoro-phenoxymethyl)-phenyl]-acrylic acid ethyl esterYield 95%

Reagents, catalysts & solvents 5

HCID 74236Tetrabutylammonium BromideCatalystHCID 167845palladium(II) acetateCatalystHCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent2×HCID 15413tert-Butyl methyl etherSolvent

Procedure

To a mixture of 1-bromo-4-fluoro-2-(2-iodo-benzyloxy)-benzene (0.29 mol, 117.4 g), sodium acetate (0.44 mol, 36.1 g, 1.5 equiv.), tetra-n-butylammonium bromide (0.29 mol, 90.3 g), palladium (II) acetate (8 mmol, 1.8 g, 3 mol %), and N-methylpyrrolidinone (900 mL) at 55-60° C., add drop wise a solution of ethyl acrylate (0.32 mol, 34.3 mL) in N-methylpyrrolidinone (200 mL). Cool the reaction mixture to room temperature and treat with water (2 L) and methyl tert-butyl ether (2 L). Pass through diatomaceous earth, add ethyl acetate (1 L), separate the layers, and wash with water (2 L). Dry the organic portion over anhydrous sodium sulfate, filter, and concentrate. Suspend the resulting solid in hexanes (1 L), refrigerate for 2 h, filter, and wash with cold hexanes (500 mL). Dry in a vacuum oven (50° C./20 mm Hg) to obtain the title compound as a pale yellow solid (104.4 g, 95%). LC-MS m/z 381.0 [M+H]+.

Workup

  1. customseparate the layers
  2. washwash with water (2 L)
  3. dry with materialDry the organic portion over anhydrous sodium sulfate
  4. filtrationfilter
  5. concentrationconcentrate
  6. filtrationfilter
  7. washwash with cold hexanes (500 mL)
  8. customDry in a vacuum oven (50° C./20 mm Hg)

Sources & evidence

ORD record
ord-6d6e3f6cd92b486ea28c86da324933a8
Source dataset
uspto-grants-2011_08
Patent number
US07994164B2

Reaction notes

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