Tetrahydrofuran → N-(4-chloro-6-fluoro-2-methoxy-3-nitrophenyl)acetamide

HRID 394442Notes

Reaction equation

HRID 394442 reaction equation
O([Si](C)(C)C)[Na].[Cl:7][C:8]1[CH:13]=[C:12]([F:14])[C:11]([NH:15][C:16](=[O:18])[CH3:17])=[C:10](F)[C:9]=1[N+:20]([O-:22])=[O:21].[O:23]1CCC[CH2:24]1>O1CCOCC1.CO>[Cl:7][C:8]1[CH:13]=[C:12]([F:14])[C:11]([NH:15][C:16](=[O:18])[CH3:17])=[C:10]([O:23][CH3:24])[C:9]=1[N+:20]([O-:22])=[O:21]

Participants

6

Reactant 3

HCID 8028TetrahydrofuranHCID 18176006N-(4-chloro-2,6-difluoro-3-nitrophenyl)acetamideHCID 178504319sodium trimethyl(oxido)silane

Product 1

HCID 18176014N-(4-chloro-6-fluoro-2-methoxy-3-nitrophenyl)acetamideYield 63%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of 72.5 g (647 mmol) of NaOSi(CH3)3 in 25 ml of tetrahydrofuran was added dropwise at approximately 20° C. to a solution of 81 g (323 mmol) of N-(4-chloro-2,6-difluoro-3-nitro-phenyl)acetamide in 490 ml of dioxane and 50 ml of methanol. The mixture was subsequently heated for two hours at reflux temperature. After cooling and concentrating, the crude product (black oil) was stirred into ice-cold 10% strength hydrochloric acid. The resulting product of value was then extracted with ethyl acetate (3 times). The combined organic phases were dried over magnesium sulfate and concentrated under reduced pressure. The residue was stirred once with water. The insoluble components were removed and washed three times with water. After drying, 52.1 g (63%) of the product of value were obtained.

Workup

  1. temperatureThe mixture was subsequently heated for two hours
  2. temperatureat reflux temperature
  3. temperatureAfter cooling
  4. concentrationconcentrating
  5. extractionThe resulting product of value was then extracted with ethyl acetate (3 times)
  6. dry with materialThe combined organic phases were dried over magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. stirringThe residue was stirred once with water
  9. customThe insoluble components were removed
  10. washwashed three times with water
  11. customAfter drying

Sources & evidence

ORD record
ord-a805e728653c4b82bbf157260d83d1d5
Source dataset
uspto-grants-2003_08
Patent number
US06602825B1

Reaction notes

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