Hydrazine hydrate (1:1) → (4R)-4-(3-chlorophenyl)-1,4,5,6-tetrahydrocyclopenta[c]pyrazole

Temperature

125 °C

(3S)-3-(3-Chlorophenyl)cyclopentanone (1.5 g, 7.71 mmol) is dissolved in isopropanol (20 mL) and stirred. tert-Butoxybis(dimethylamino)methane (1.91 mL, 9.25 mmol) is added drop wise to the reaction. The reaction is heated to 125° C. for 12 hours. It is then cooled to room temperature and concentrated to dryness. The residue is diluted with isopropanol (20 mL). Hydrazine hydrate (0.37 mL, 11.56 mmol) is added to the reaction and the reaction is heated to 100° C. for 5 hours. The reaction is concentrated in vacuo and the residue is purified via silica gel chromatography, eluting with 20% ethyl acetate in hexanes to obtain the title product (1.099 g) as a yellow film. This material is further purified via chiral chromatography, employing a Chiralpak AD-H column, eluting with 20% methanol/CO2, a flow rate of 70 mL/min, and UV detection at 225 nM. The title compound (0.442 g, 26.2%) is isolated as a clear oil. ES/MS (m/z) 219.0 (M+1).

1. customwise to the reaction
2. temperatureIt is then cooled to room temperature
3. concentrationconcentrated to dryness
4. additionThe residue is diluted with isopropanol (20 mL)
5. temperaturethe reaction is heated to 100° C. for 5 hours
6. concentrationThe reaction is concentrated in vacuo
7. customthe residue is purified via silica gel chromatography
8. washeluting with 20% ethyl acetate in hexanes

ORD record

ord-6d23b3d2ab5148b896ed7bd39fc245a7

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08778984B2