Hydrazine → 5-Cyclobutyl-1H-pyrazol-3-amine

Temperature

75 °C

To an aliquot of the crude 3-cyclobutyl-3-oxo-propionitrile (10.0 g, 81.3 mmol) prepared above in EtOH (300 mL) was added hydrazine. The resulting mixture was heated to 75° C. (oil bath). After 14 hr, the reaction was cooled to room temperature and concentrated under reduced pressure. The resulting oil was taken up in EtOAc and washed with saturated aqueous NaHCO3 solution. The layers were separated and the aqueous layer was extracted with EtOAc. The combined organic layers were dried over MgSO4, filtered through a pad of diatomaceous earth, and concentrated under reduced pressure. Purification of this material was accomplished by flash column chromatography on a Biotage® 75S MPLC system (A Dynax Corp., Charlottesville, Va.), eluting with 100 EtOAc (2 L) and 10% MeOH/CH2Cl2 (2 L). The product-containing fractions were collected and concentrated to give the title compound (10.0 g, 91% yield) as a brown oil. 400 MHz 1H NMR (CDCl3) d 5.47 (s, 1H), 5.25 (bs, 3H), 3.40 (dddd, J=8.3, 8.3, 8.3, 8.3 Hz, 1H), 2.34-2.27 (m, 2H), 2.16-1.88 (m, 4H). LRMS m/z (APCI+) 138 (M+1).

1. temperaturethe reaction was cooled to room temperature
2. concentrationconcentrated under reduced pressure
3. washwashed with saturated aqueous NaHCO3 solution
4. customThe layers were separated
5. extractionthe aqueous layer was extracted with EtOAc
6. dry with materialThe combined organic layers were dried over MgSO4
7. filtrationfiltered through a pad of diatomaceous earth
8. concentrationconcentrated under reduced pressure
9. customPurification of this material
10. wash), eluting with 100 EtOAc (2 L) and 10% MeOH/CH2Cl2 (2 L)
11. customThe product-containing fractions were collected
12. concentrationconcentrated

ORD record

ord-a13bd5a7b169410998df822eb039c7e5

Source dataset

uspto-grants-2007_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07300944B2