Water → HCID 58016865, compound

HRID 1926905Notes

Reaction equation

HRID 1926905 reaction equation
[CH2:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9](=O)[CH:10]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[F:18])[OH:11])=[CH:5][CH:4]=1)[CH3:2].[C:20](#[N:24])[CH2:21][C:22]#[N:23].C(NCC)C.O>CN(C=O)C.C(OCC)(=O)C>[NH2:24][C:20]1[O:11][C:10]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[F:18])=[C:9]([C:6]2[CH:7]=[CH:8][C:3]([CH2:1][CH3:2])=[CH:4][CH:5]=2)[C:21]=1[C:22]#[N:23]

Participants

7

Reactant 4

HCID 962WaterHCID 8010Malononitrile2×HCID 8021Diethylamine2×HCID 58016960HCID 58016960, compound

Product 1

HCID 58016865HCID 58016865, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent2×

Procedure

Put 50 g (0.19 mol) 1-(4-ethylphenyl)-2-(2-fluorophenyl)-2-hydroxyethanone and 17 g (0.25 mol) malononitrile in 93 ml DMF. After stirring for five minutes, add 17 ml (12 g, 0.12 mol) diethylamine, cooling with ice. Stir the reaction mixture for 1 h with ice cooling. Then leave to warm to room temperature and stir for 4 h at this temperature. After adding 500 ml water and stirring for 30 min, decant the aqueous phase. Add 500 ml water again and decant again, obtaining an oily residue, which is dissolved in ethyl acetate, dried over sodium sulphate and filtered. Concentrate the filtrate by vacuum evaporation. According to DC analysis (solvent: cyclohexane/ethyl acetate 4:1), the residue still contains 1-(4-ethylphenyl)-2-(2-fluorophenyl)-2-hydroxyethanone. Therefore, the residue is again reacted in 90 ml DMF with 5.5 g (0.08 mol) malononitrile and 10 ml (7 g, 0.10 mol) diethylamine in accordance with the above procedure. Add the reaction mixture to 500 ml ethyl acetate and wash three times with 300 ml water each time and once with 300 ml satd. sodium chloride solution. Dry the organic phase over sodium sulphate, and filter. Concentrate the filtrate by vacuum evaporation. Purify the residue by flash chromatography on silica gel (solvent: cyclohexane/ethyl acetate 3:1). 36 g (61% of theor.) of the title compound is obtained, and is reacted without further characterization.

Workup

  1. temperaturecooling with ice
  2. stirringStir the reaction mixture for 1 h with ice cooling
  3. customThen leave
  4. stirringstir for 4 h at this temperature
  5. stirringstirring for 30 min
  6. customdecant the aqueous phase
  7. additionAdd 500 ml water again
  8. customdecant again
  9. customobtaining an oily residue, which
  10. dry with materialdried over sodium sulphate
  11. filtrationfiltered
  12. concentrationConcentrate the filtrate
  13. customby vacuum evaporation
  14. washwash three times with 300 ml water each time
  15. dry with materialDry the organic phase over sodium sulphate
  16. filtrationfilter
  17. concentrationConcentrate the filtrate
  18. customby vacuum evaporation
  19. customPurify the residue by flash chromatography on silica gel (solvent: cyclohexane/ethyl acetate 3:1)

Sources & evidence

ORD record
ord-2aa761d3df4d43b8bd10127b29f7f877
Source dataset
uspto-grants-2012_05
Patent number
US08183246B2

Reaction notes

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