Dichloromethane → HCID 22769937, compound

Cyclohexylhydrazine hydrochloride (700 g, 4643 mmol) was added to a stirred solution of DCM (3000 ml) and ice cold 2M NaOH solution (1778 mL, 3556 mmol) and this was stirred for 10 minutes at RT. The phases were separated and the aqueous layer was washed with DCM (4×2000 ml). The combined organic extracts were dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure to give a yellow solid. The solid cyclohexylhydrazine (406 g, 3556 mmol) was dissolved in water (1300 mL) and acetic acid (1300 mL) and treated with ethyl acetoacetate (450 mL, 3556 mmol). The reaction mixture was heated to 85° C. and stirred for 1 hour. The resulting mixture was concentrated to dryness under reduced pressure and the residue was dissolved in DCM (3000 ml) and water (1000 ml). The mixture was neutralized with 2M potassium carbonate to pH>9, the resulting phases were separated and the organic extract was washed with brine (1×2 L). The first aqueous layer was saturated with sodium chloride and both aqueous phases washed with DCM (4×2 L). The combined organic extracts were dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give a beige solid. The crude product was ground to a powder, TBME (2000 ml) was added and the mixture was stirred at 50° C. for 1 hour, followed by 1 hour at room temperature. The resulting solid was collected by filtration, washed with TBME (4×500 ml) and dried under vacuum at 45° C. for 16 hours to yield the title compound as off-white crystals.

1. customThe phases were separated
2. washthe aqueous layer was washed with DCM (4×2000 ml)
3. dry with materialThe combined organic extracts were dried over anhydrous sodium sulphate
4. filtrationfiltered
5. concentrationconcentrated under reduced pressure
6. customto give a yellow solid
7. temperatureThe reaction mixture was heated to 85° C.
8. stirringstirred for 1 hour
9. concentrationThe resulting mixture was concentrated to dryness under reduced pressure
10. dissolutionthe residue was dissolved in DCM (3000 ml)
11. customthe resulting phases were separated
12. extractionthe organic extract
13. washwas washed with brine (1×2 L)
14. washboth aqueous phases washed with DCM (4×2 L)
15. dry with materialThe combined organic extracts were dried over anhydrous sodium sulfate
16. filtrationfiltered
17. concentrationconcentrated under reduced pressure
18. customto give a beige solid
19. additionwas added
20. stirringthe mixture was stirred at 50° C. for 1 hour
21. waitfollowed by 1 hour at room temperature
22. filtrationThe resulting solid was collected by filtration
23. washwashed with TBME (4×500 ml)
24. customdried under vacuum at 45° C. for 16 hours

ORD record

ord-e3799a371e774ec49ba79a781ccb2af7

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09403833B2