Methyl iodide → 2-(2-Isopropyl-4-methoxy-5-methyl-phenoxy)-3-methoxy-acrylic acid ethyl ester

HRID 38348Notes

Reaction equation

HRID 38348 reaction equation
[CH2:1]([O:3][C:4](=[O:19])[CH2:5][O:6][C:7]1[CH:12]=[C:11]([CH3:13])[C:10]([O:14][CH3:15])=[CH:9][C:8]=1[CH:16]([CH3:18])[CH3:17])[CH3:2].[H-].[Na+].[CH:22]([O:24][CH2:25]C)=O.IC>COCCOC>[CH2:1]([O:3][C:4](=[O:19])[C:5]([O:6][C:7]1[CH:12]=[C:11]([CH3:13])[C:10]([O:14][CH3:15])=[CH:9][C:8]=1[CH:16]([CH3:18])[CH3:17])=[CH:22][O:24][CH3:25])[CH3:2]

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 8025Ethyl formateHCID 24758Sodium hydrideHCID 59598614(2-Isopropyl-4-methoxy-5-methyl-phenoxy)-acetic acid ethyl ester

Product 1

HCID 670534762-(2-Isopropyl-4-methoxy-5-methyl-phenoxy)-3-methoxy-acrylic acid ethyl esterYield 23.2%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
85 °C

Procedure

To a solution of (2-isopropyl-4-methoxy-5-methyl-phenoxy)-acetic acid ethyl ester (4.42 g, 16.6 mmol) in anhydrous 1,2-dimethoxy ethane (60 ml) was added sodium hydride (60% in mineral oil, 3.5 g, 87.5 mmol) at room temperature. After 5 minutes of stirring, ethyl formate (40 ml, 495 mmol) was added. The mixture was heated at 85° C. for 7 hours. After cooling to room temperature, iodomethane was added and stirring was continued overnight. Solvent was concentrated under reduced pressure and the residue was partitioned between ethyl acetate and water. The organic phase was washed with brine and dried over anhydrous sodium sulfate. After removal of drying agent, the organic solution was concentrated under reduced pressure. The residue was purified with silica gel chromatography (10% to 30% ethyl acetate in hexane) to yield 2-(2-isopropyl-4-methoxy-5-methyl-phenoxy)-3-methoxy-acrylic acid ethyl ester as a pale yellow oil (1.19 g, 23%).

Workup

  1. temperatureAfter cooling to room temperature
  2. stirringstirring
  3. waitwas continued overnight
  4. concentrationSolvent was concentrated under reduced pressure
  5. customthe residue was partitioned between ethyl acetate and water
  6. washThe organic phase was washed with brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. customAfter removal
  9. customof drying agent
  10. concentrationthe organic solution was concentrated under reduced pressure
  11. customThe residue was purified with silica gel chromatography (10% to 30% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-5eddfb474ea64574adfd0ed09d025926
Source dataset
uspto-grants-2013_09
Patent number
US08524725B2

Reaction notes

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