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

Participants

Reaction Conditions

Reaction Steps

(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).

Provenance & Evidence