Methyl iodide → 2-(5-Bromo-2-isopropyl-4-methoxy-phenoxy)-3-methoxy-acrylonitrile

HRID 38326Notes

Reaction equation

HRID 38326 reaction equation
[H-].[Na+].[Br:3][C:4]1[C:5]([O:17][CH3:18])=[CH:6][C:7]([CH:14]([CH3:16])[CH3:15])=[C:8]([CH:13]=1)[O:9][CH2:10][C:11]#[N:12].[CH:19]([O:21][CH2:22]C)=O.IC>>[Br:3][C:4]1[C:5]([O:17][CH3:18])=[CH:6][C:7]([CH:14]([CH3:16])[CH3:15])=[C:8]([CH:13]=1)[O:9][C:10](=[CH:19][O:21][CH3:22])[C:11]#[N:12]

Participants

5

Reactant 4

HCID 6328Methyl iodideHCID 8025Ethyl formateHCID 24758Sodium hydrideHCID 59598690(5-Bromo-2-isopropyl-4-methoxy-phenoxy)-acetonitrile

Product 1

HCID 670533812-(5-Bromo-2-isopropyl-4-methoxy-phenoxy)-3-methoxy-acrylonitrileYield 48.2%

Conditions

Temperature
80 °C

Procedure

Sodium hydride (0.122 g, 5.0 mmol, 60% w/w) was washed with dry hexanes and evaporated under a stream of nitrogen. 10 mL THF was added and the mixture was cooled to 0° C. (5-Bromo-2-isopropyl-4-methoxy-phenoxy)-acetonitrile (0.577 g, 2.03 mmol) was added in portions. After 30 min ethyl formate (4.9 mL, 60.9 mmol) was added and the solution was warmed to 80° C. After 4.5 hours the mixture was cooled and 5.0 mL iodomethane was added in one portion. After 16 hours the solution was quenched with H2O, concentrated in vacuo, extracted with ethyl acetate, washed with H2O and then washed with brine. The combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo. Purification via flash chromatography (9:1 hexane/ethyl acetate) afforded 2-(5-bromo-2-isopropyl-4-methoxy-phenoxy)-3-methoxy-acrylonitrile (0.319 g, 48%) as a white solid.

Workup

  1. customevaporated under a stream of nitrogen
  2. addition10 mL THF was added
  3. additionwas added in portions
  4. temperatureAfter 4.5 hours the mixture was cooled
  5. customAfter 16 hours the solution was quenched with H2O
  6. concentrationconcentrated in vacuo
  7. extractionextracted with ethyl acetate
  8. washwashed with H2O
  9. washwashed with brine
  10. dry with materialThe combined organic layers were dried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customPurification via flash chromatography (9:1 hexane/ethyl acetate)

Sources & evidence

ORD record
ord-3657d13a7fe94bbfb7a63d5ff1265f5c
Source dataset
uspto-grants-2013_09
Patent number
US08524725B2

Reaction notes

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