Hydrochloric Acid → 4,4-Difluoro-1-[4-(morpholino)phenyl]-butane-1,3-dione

HRID 864539Notes

Reaction equation

HRID 864539 reaction equation
[F:1][CH:2]([F:8])[C:3](OCC)=[O:4].C[O-].[Na+].[O:12]1[CH2:17][CH2:16][N:15]([C:18]2[CH:23]=[CH:22][C:21]([C:24](=[O:26])[CH3:25])=[CH:20][CH:19]=2)[CH2:14][CH2:13]1.Cl>C1COCC1>[F:1][CH:2]([F:8])[C:3](=[O:4])[CH2:25][C:24]([C:21]1[CH:20]=[CH:19][C:18]([N:15]2[CH2:14][CH2:13][O:12][CH2:17][CH2:16]2)=[CH:23][CH:22]=1)=[O:26]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 9961Ethyl difluoroacetateHCID 383624-MorpholinoacetophenoneHCID 10942334Sodium Methoxide

Product 1

HCID 189203754,4-Difluoro-1-[4-(morpholino)phenyl]-butane-1,3-dioneYield 91.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Ethyl difluoroacetate (2.30 g, 18.5 mmol) was placed in a 100 mL round bottom flask and dissolved in THF (25 mL). To the stirred solution was added 25 weight % sodium methoxide (4.90 g, 22.6 mmol) followed by 4'-morpholinoacetophenone (3.45 g, 16.8 mmol). The reaction was stirred at room temperature overnight (15.8 hours), then treated with 3N HCl (13 mL). The reaction was extracted with ethyl acetate (20 mL), washed with brine (20 mL), dried over MgSO4, and concentrated in vacuo to give a green solid (4.36 g) which was recrystallized from methylene chloride/isooctane to give the diketone as a yellow solid (3.27 g, mp 102°-3° C., 69%). 1H NMR (CDCl3) 300 MHz 15.80 (br s, 1H), 7.86 (d, J=9.1 Hz, 2H), 6.90 (d, J=9.1 Hz, 2H), 6.46 (s, 1H), 5.99 (t, J=54.4 Hz, 1H), 3.84 (m, 4 H), 3.36 (m, 4H); 19F NMR (CDCl3) 300 MHz: -126.75 (d); M+283.

Workup

  1. extractionThe reaction was extracted with ethyl acetate (20 mL)
  2. washwashed with brine (20 mL)
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f60ac0e0b82a4517836364a8d45fa074
Source dataset
uspto-grants-1996_10
Patent number
US05563165

Reaction notes

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