Tetrahydrofuran → Ethyl 3-(4-fluoroanilino)-3-oxopropanoate

HRID 893190Notes

Reaction equation

HRID 893190 reaction equation
[F:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][CH:3]=1.C(N([CH2:14][CH3:15])CC)C.C([CH:18]([C:22](Cl)=[O:23])[C:19](Cl)=[O:20])C.[O:25]1CCCC1>>[F:1][C:2]1[CH:8]=[CH:7][C:5]([NH:6][C:22](=[O:23])[CH2:18][C:19]([O:20][CH2:14][CH3:15])=[O:25])=[CH:4][CH:3]=1

Participants

5

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 8471TriethylamineHCID 97314-FluoroanilineHCID 109209242-Ethylpropanedioyl dichloride

Product 1

HCID 17097465Ethyl 3-(4-fluoroanilino)-3-oxopropanoate

Procedure

Into a nitrogen-purged, air-stirred reaction flask was charged 4.44 grams (0.04 mol) of 4-fluoroaniline, 4.05 grams (0.04 mole) of triethylamine and 200 milliliters of tetrahydrofuran solvent. A 6.02 gram (0.04 mol) portion of ethyl malonyl chloride was then added rapidly by a dropping funnel to the mixture with good stirring at room temperature followed by a few milliliters of tetrahydrofuran as a rinse. The temperature of the stirred mixture rose to 42° C. and a white precipitate of triethylamine hydrochloride separate therefrom. The mixture was then stirred at ambient temperature for about 2 hours and the triethylamine hydrochloride filtered off, washed with solvent and dried to give 5.2 grams (0.04 mole). The filtrate was freed of solvent on a rotary evaporator and the resulting purple solid dissolved in methylene chloride, which solution was washed in succession with 2N HCl (3×75 milliliters), and water (2×75 milliliters), and then dried over magnesium sulfate and solvent vacuum stripped to give a crude solid product. Recrystallization from ethyl acetate-cyclohexane followed by flash column chromatography gave 3.47 grams (0.015 mole) of ethyl 3-[(4-fluorophenyl)amino]-3-oxopropanoate having a melting point of 68° C-71° C.

Workup

  1. customInto a nitrogen-purged
  2. customreaction flask
  3. stirringwith good stirring at room temperature
  4. customrose to 42° C.
  5. customa white precipitate of triethylamine hydrochloride separate
  6. stirringThe mixture was then stirred at ambient temperature for about 2 hours
  7. filtrationthe triethylamine hydrochloride filtered off
  8. washwashed with solvent
  9. customdried
  10. customto give 5.2 grams (0.04 mole)
  11. customThe filtrate was freed of solvent on a rotary evaporator
  12. dissolutionthe resulting purple solid dissolved in methylene chloride
  13. washwhich solution was washed in succession with 2N HCl (3×75 milliliters), and water (2×75 milliliters)
  14. dry with materialdried over magnesium sulfate and solvent vacuum
  15. customto give a crude solid product
  16. customRecrystallization from ethyl acetate-cyclohexane

Sources & evidence

ORD record
ord-1363dfe4079f4ea29fe1092eb75ef3cd
Source dataset
uspto-grants-1992_06
Patent number
US05123951

Reaction notes

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