Hydrazine hydrate (1:1) → HCID 66643279, compound

Temperature

85 °C

To a solution of Example 99A (10.0 g, 41.3 mmol) in EtOH (85 mL) was added hydrazine hydrate (3.02 mL, 61.9 mmol). The mixture was warmed to reflux (85° C.) and was allowed to stir for 20 hours. The mixture was cooled to ambient temperature then 4,4-dimethyl-3-oxopentanenitrile (7.78 g, 61.9 mmol) was added and the mixture was again warmed to reflux (85° C.) and was allowed to stir for 4 hours then the mixture was concentrated under reduced pressure and the residue was dissolved in CH2Cl2 (100 mL) and saturated aqueous NaHCO3 (50 mL) was added slowly. The layers were separated and the aqueous phase was extracted with CH2Cl2 (3×10 mL). The combined organic extracts were dried over Na2SO4, filtered and concentrated under reduced pressure. Purification by column chromatography (SiO2, 50% hexanes/EtOAc) provided the title compound (7.6 g, 36.3 mmol, 88% yield). MS (DCI/NH3) m/z 210 (M+H)+.

1. temperatureThe mixture was warmed
2. temperatureThe mixture was cooled to ambient temperature
3. temperaturethe mixture was again warmed
4. temperatureto reflux (85° C.)
5. stirringto stir for 4 hours
6. concentrationthe mixture was concentrated under reduced pressure
7. dissolutionthe residue was dissolved in CH2Cl2 (100 mL)
8. additionsaturated aqueous NaHCO3 (50 mL) was added slowly
9. customThe layers were separated
10. extractionthe aqueous phase was extracted with CH2Cl2 (3×10 mL)
11. dry with materialThe combined organic extracts were dried over Na2SO4
12. filtrationfiltered
13. concentrationconcentrated under reduced pressure
14. customPurification by column chromatography (SiO2, 50% hexanes/EtOAc)

ORD record

ord-fae0b38849a043cf87b34dff5a794da4

Source dataset

uspto-grants-2012_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08188135B2