Water → 2-Cyclohexyl-1,2-dihydro-1,5-dimethyl-3H-pyrazol-3-one

HRID 1478820Notes

Reaction equation

HRID 1478820 reaction equation
[CH:1]1([N:7]2[C:11](=[O:12])[CH:10]=[C:9]([CH3:13])[NH:8]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.CI.O.[C:17](=O)([O-])[O-].[K+].[K+]>CN(C)C=O.C(Cl)Cl>[CH:1]1([N:7]2[C:11](=[O:12])[CH:10]=[C:9]([CH3:13])[N:8]2[CH3:17])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 962WaterHCID 6328Methyl iodide2×HCID 11430Potassium CarbonateHCID 22769937HCID 22769937, compound

Product 1

HCID 204640012-Cyclohexyl-1,2-dihydro-1,5-dimethyl-3H-pyrazol-3-one

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
40 °C

Procedure

A suspension of 2-cyclohexyl-5-methyl-1H-pyrazol-3(2H)-one (525 g, 2834 mmol) in N,N-dimethylformamide (2200 mL) was heated to 40° C. and methyl iodide (532 mL, 8502 mmol) was added. The reaction mixture was heated to 70° C. for 20 h. Further methyl iodide (177 mL, 2834 mmol) was added and the mixture was stirred at 75° C. for 3.5 hours, then 80° C. for 20 hours. The resulting mixture was concentrated under reduced pressure and the residue was triturated with TBME (2000 ml). The product was collected by filtration, washing with TBME (5×500 ml) to give a solid which was suspended in DCM (2500 ml) and water (500 ml) and neutralized with 2M potassium carbonate solution (1700 ml) to pH>9. The phases were separated and the aqueous layer was extracted with DCM (3×500 ml). The organic extracts were washed with brine (1000 ml) and concentrated under reduced pressure. The resulting residue was dissolved in ethyl acetate (2000 ml), dried over anhydrous sodium sulfate and filtered through 200 g of silica gel (40-63 μm), washing with ethyl acetate/methanol 9:1 (7×300 ml). The filtrate was concentrated under reduced pressure and to give the title compound as a brown oil.

Workup

  1. temperatureThe reaction mixture was heated to 70° C. for 20 h
  2. wait80° C. for 20 hours
  3. concentrationThe resulting mixture was concentrated under reduced pressure
  4. customthe residue was triturated with TBME (2000 ml)
  5. filtrationThe product was collected by filtration
  6. washwashing with TBME (5×500 ml)
  7. customto give a solid which
  8. customThe phases were separated
  9. extractionthe aqueous layer was extracted with DCM (3×500 ml)
  10. washThe organic extracts were washed with brine (1000 ml)
  11. concentrationconcentrated under reduced pressure
  12. dissolutionThe resulting residue was dissolved in ethyl acetate (2000 ml)
  13. dry with materialdried over anhydrous sodium sulfate
  14. filtrationfiltered through 200 g of silica gel (40-63 μm)
  15. washwashing with ethyl acetate/methanol 9:1 (7×300 ml)
  16. concentrationThe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-799999d4b8c241798e26d90fe66ad293
Source dataset
uspto-grants-2016_08
Patent number
US09403833B2

Reaction notes

Loading…