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

Temperature

40 °C

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 hours. 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. The isolated solid was suspended in DCM (2500 mL) and water (500 mL) and the pH adjusted to pH 9 using an aqueous 2M K2CO3 solution (1700 mL). The phases were separated and the aqueous layer was extracted with DCM (3×500 mL). The combined 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), eluting with 10% MeOH in EtOAc (7×300 mL). The filtrate was concentrated under reduced pressure and dried at 65° C. to afford the title compound;

1. temperatureThe reaction mixture was heated to 70° C. for 20 hours
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
8. customThe phases were separated
9. extractionthe aqueous layer was extracted with DCM (3×500 mL)
10. washThe combined 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. washeluting with 10% MeOH in EtOAc (7×300 mL)
16. concentrationThe filtrate was concentrated under reduced pressure
17. customdried at 65° C.

ORD record

ord-0c59b9c4490243c4bc3e49a63d7cc73b

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09403810B2