Phenol → (E)-ethyl 3-(3,5-difluoro-4-phenoxyphenyl)-2-methylacrylate

HRID 45689Notes

Reaction equation

HRID 45689 reaction equation
[CH3:1]/[C:2](=[CH:8]\[C:9]1[CH:14]=[C:13]([F:15])[C:12](F)=[C:11]([F:17])[CH:10]=1)/[C:3]([O:5][CH2:6][CH3:7])=[O:4].[C:18]1([OH:24])[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[F:15][C:13]1[CH:14]=[C:9](/[CH:8]=[C:2](\[CH3:1])/[C:3]([O:5][CH2:6][CH3:7])=[O:4])[CH:10]=[C:11]([F:17])[C:12]=1[O:24][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

5

Reactant 3

HCID 996PhenolHCID 11430Potassium CarbonateHCID 12016766(E)-ethyl 2-methyl-3-(3,4,5-trifluorophenyl)acrylate2×

Product 1

HCID 70876774(E)-ethyl 3-(3,5-difluoro-4-phenoxyphenyl)-2-methylacrylateYield 89%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (E)-ethyl 2-methyl-3-(3,4,5-trifluorophenyl)acrylate (Intermediate 41.1, 6.0 g, 24.56 mmol) in dry DMF (25 mL) under N2 was added phenol (2.774 g, 29.5 mmol) and K2CO3 (10.2 g, 73.68 mmol). The resulting solution was brought to 120° C. and stirred for 3 hours at which point TLC indicated complete conversion. The solvent was removed by rotary evaporation and the resulting residue brought up in EtOAc (200 mL) and washed with water (2×200 mL), 1N NaOH (2×200 mL) and brine (200 mL). The organic layer was dried over Na2SO4 and concentrated to yield 6.94 g (89%) of the title compound as tan crystals.

Workup

  1. customwas brought to 120° C.
  2. customThe solvent was removed by rotary evaporation
  3. washwashed with water (2×200 mL), 1N NaOH (2×200 mL) and brine (200 mL)
  4. dry with materialThe organic layer was dried over Na2SO4
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-8fa926e9cba24ff7b86b4861a67e6455
Source dataset
uspto-grants-2013_09
Patent number
US08541448B2

Reaction notes

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