Malononitrile → HCID 58016904, compound

HRID 2189063Notes

Reaction equation

HRID 2189063 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]([OH:19])[C:9]([C:11]1[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=1)=O.[C:20](#[N:24])[CH2:21][C:22]#[N:23].C(N(CC)CC)C.C(OCC)(=O)C>C1COCC1>[NH2:24][C:20]1[O:19][C:8]([C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[F:1])=[C:9]([C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=2)[C:21]=1[C:22]#[N:23]

Participants

6

Reactant 4

HCID 8010Malononitrile2×HCID 8471Triethylamine2×HCID 8857Ethyl AcetateHCID 58016924HCID 58016924, compound2×

Product 1

HCID 58016904HCID 58016904, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Put 84 g (0.32 mol) 2-(2-fluorophenyl)-2-hydroxy-1-(4-methoxyphenyl)ethanone and 32 g (0.48 mol) malononitrile in 153 ml THF. After stirring for five minutes, add 49 ml (36 g, 0.36 mol) triethylamine, with ice cooling. Stir the reaction mixture for 1 h with ice cooling. Then leave the reaction mixture to warm to room temperature and stir for 4 h at this temperature. After adding 1000 ml ethyl acetate, wash the organic phase five times with 300 ml water, dry over sodium sulphate and filter. Concentrate the filtrate by vacuum evaporation. Take up the residue in dichloromethane and purify by flash chromatography on silica gel (solvent: dichloromethane/methanol 70:1, then cyclohexane/ethyl acetate 2:1). 37 g (0.11 mol) of 2-(2-fluorophenyl)-2-hydroxy-1-(4-methoxyphenyl)ethanone thus recovered is again reacted with 14 g (0.03 mol) malononitrile and 21 ml (15 g, 0.15 mol) triethylamine in 67 ml THF in accordance with the above procedure. A total of 70 g (52% purity, 36% of theor.) of the target compound is obtained.

Workup

  1. stirringStir the reaction mixture for 1 h with ice cooling
  2. customThen leave the reaction mixture
  3. stirringstir for 4 h at this temperature
  4. washwash the organic phase five times with 300 ml water
  5. dry with materialdry over sodium sulphate
  6. filtrationfilter
  7. concentrationConcentrate the filtrate
  8. customby vacuum evaporation
  9. custompurify by flash chromatography on silica gel (solvent
  10. customA total of 70 g (52% purity, 36% of theor.) of the target compound is obtained

Sources & evidence

ORD record
ord-c831af51b69443bcb55386f611ace57a
Source dataset
uspto-grants-2012_12
Patent number
US08324222B2

Reaction notes

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