Sodium hydride → 2-(3-Fluoro-phenyl)-cyclopropanecarboxylic acid methoxy-methyl-amide

HRID 857012Notes

Reaction equation

HRID 857012 reaction equation
[H-].[Na+].[I-].[CH3:4][S+](C)(C)=O.[F:9][C:10]1[CH:11]=[C:12]([CH:16]=[CH:17][C:18]([N:20]([O:22][CH3:23])[CH3:21])=[O:19])[CH:13]=[CH:14][CH:15]=1>CN(C=O)C>[CH3:23][O:22][N:20]([CH3:21])[C:18]([CH:17]1[CH2:4][CH:16]1[C:12]1[CH:13]=[CH:14][CH:15]=[C:10]([F:9])[CH:11]=1)=[O:19]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 74498Sulfoxonium, trimethyl-, iodide (1:1)HCID 730107483-(3-fluoro-phenyl)-N-methoxy-N-methyl-acrylamide

Product 1

HCID 587594712-(3-Fluoro-phenyl)-cyclopropanecarboxylic acid methoxy-methyl-amideYield 84.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

NaH (8 g, 60% oil dispersion) was added to a suspension of trimethylsulfoxonium iodide (44 g) in DMF (150 mL) at 0° C. The resulting mixture was allowed to warm to room temperature and stirred for 0.5 h. A solution of 3-(3-fluoro-phenyl)-N-methoxy-N-methyl-acrylamide (20 g) was added to the above reaction mixture at 0° C., and the resulting reaction was allowed to warm to room temperature and stirred for 2 h. The reaction was quenched with water and the aqueous layer was extracted with CH2Cl2. The combined organic layers were washed with brine, dried over MgSO4, and concentrated in vacuo to give a residue. The residue was purified by flash chromatography over silica gel (elution with 50% hexanes in ethyl acetate) to give the title compound (18 g) as an oil.

Workup

  1. customthe resulting reaction
  2. temperatureto warm to room temperature
  3. stirringstirred for 2 h
  4. customThe reaction was quenched with water
  5. extractionthe aqueous layer was extracted with CH2Cl2
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated in vacuo
  9. customto give a residue
  10. customThe residue was purified by flash chromatography over silica gel (elution with 50% hexanes in ethyl acetate)

Sources & evidence

ORD record
ord-2a9adb146a8c4d5c9e2f4230e95eeef7
Source dataset
uspto-grants-2006_12
Patent number
US07144881B2

Reaction notes

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