Hydrochloric Acid → HCID 67287673, compound

HRID 1626501Notes

Reaction equation

HRID 1626501 reaction equation
[Na].Cl.[F:3][C:4]1[CH:5]=[C:6]([NH:11][NH2:12])[CH:7]=[CH:8][C:9]=1[F:10].C(O/[CH:16]=[CH:17]/[C:18]#[N:19])C.Cl.[OH-].[Na+]>O.C(O)C>[F:3][C:4]1[CH:5]=[C:6]([N:11]2[CH:16]=[CH:17][C:18]([NH2:19])=[N:12]2)[CH:7]=[CH:8][C:9]=1[F:10]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 5324714(2E)-3-Ethoxy-2-propenenitrileHCID 5360545SodiumHCID 24721344(3,4-Difluorophenyl)hydrazine--hydrogen chloride (1/1)

Product 1

HCID 67287673HCID 67287673, compoundYield 23.1%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

To ethanol (28 ml) was added sodium (0.407 g, 17.7 mmol), and the mixture was stirred about 30 minutes. To this, (3,4-difluorophenyl)hydrazine hydrochloride (1.00 g, 5.54 mmol) and (E)-3-ethoxyacrylonitrile (0.912 ml, 8.86 mmol) were added, and the reaction was heated to reflux for 16 hours. The reaction was diluted with water (30 ml) and acidified to pH 3 with 5M hydrochloric acid. The reaction was allowed to stir at ambient temperature for another 2 hours and was then neutralized (pH 7) by the addition of 5M sodium hydroxide. The reaction was concentrated to remove most of the ethanol. The resulting suspension was extracted twice with EtOAc, and the combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified by silica gel chromatography, eluting with a linear gradient of 20-100% EtOAc/hexanes to yield the desired product (0.250 g, 1.28 mmol, 23.1% yield).

Workup

  1. temperaturethe reaction was heated
  2. temperatureto reflux for 16 hours
  3. stirringto stir at ambient temperature for another 2 hours
  4. concentrationThe reaction was concentrated
  5. customto remove most of the ethanol
  6. extractionThe resulting suspension was extracted twice with EtOAc
  7. dry with materialthe combined organic layers were dried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude product was purified by silica gel chromatography
  11. washeluting with a linear gradient of 20-100% EtOAc/hexanes

Sources & evidence

ORD record
ord-02d955df87724f3981c77a3c54c0e4c8
Source dataset
uspto-grants-2014_07
Patent number
US08785445B2

Reaction notes

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