Methyl iodide → Methyl 3-(2,4-difluorophenyl)acrylate

HRID 1992660Notes

Reaction equation

HRID 1992660 reaction equation
[F:1][C:2]1[CH:12]=[C:11]([F:13])[CH:10]=[CH:9][C:3]=1[CH:4]=[CH:5][C:6]([OH:8])=[O:7].[C:14](=O)([O-])[O-].[K+].[K+].IC>CN(C)C=O>[F:1][C:2]1[CH:12]=[C:11]([F:13])[CH:10]=[CH:9][C:3]=1/[CH:4]=[CH:5]/[C:6]([O:8][CH3:14])=[O:7]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 6035023-(2,4-Difluorophenyl)acrylic Acid

Product 1

HCID 15276473Methyl 3-(2,4-difluorophenyl)acrylateYield 77%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2,4-difluorocinnamic acid (20 g, 135 mmol) in N,N-dimethylformamide (500 mL) at room temperature under dry nitrogen was added potassium carbonate (90 g, 675 mmol) then iodomethane (21 mL, 337.5 mmol). The resulting mixture was stirred at room temperature under dry nitrogen for 7 hours before being quenched by the addition of water (1 L) and extracted with diethyl ether (3×200 mL). The combined organic extracts were dried over magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified by an automated flash column chromatography system (CombiFlash® Separation System Sg 100c by Isco) using a pre-packed column (Redisep™ Disposable Columns for Flash Chromatography by Isco, 120 g column) eluting with 2% ethyl acetate in pentane increasing polarity in a linear gradient to 10% ethyl acetate in pentane over 1 hour to afford the title compound as a white solid (20.5 g, 77%). 1H NMR (400 MHz, CDCl3) δH 3.80 (3H, s), 6.50 (1H, d), 6.85 (1H, m), 7.50 (1H, m), 7.75 (1H, d); LRMS (APCI) 216 [MNH4+], 199 [MH+].

Workup

  1. custombefore being quenched by the addition of water (1 L)
  2. extractionextracted with diethyl ether (3×200 mL)
  3. dry with materialThe combined organic extracts were dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by an automated flash column chromatography system (CombiFlash® Separation System Sg 100c by Isco)
  7. washeluting with 2% ethyl acetate in pentane increasing polarity in a linear gradient to 10% ethyl acetate in pentane over 1 hour

Sources & evidence

ORD record
ord-b49b375c995440309c4dab543b6ecb0f
Source dataset
uspto-grants-2010_01
Patent number
US07649002B2

Reaction notes

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