Hydrazine hydrate (1:1) → 6-butyl-5-(4-cyclohexyloxy-phenyl)-4-trifluoromethyl-2H-pyridazin-3-one

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of 3-(4-cyclohexyloxy-phenyl)-4-oxo-2-trifluoromethyl-oct-2-enoic acid methyl ester (3.40 mmol, 1.4 g) in glacial acetic acid (3 mL) was added hydrazine hydrate (61.7 mmol, 3 mL) and the reaction was heated at 100° C. for 12 h. After cooling, the volatiles were under reduced pressure to give 1.6 g of crude 6-butyl-5-(4-cyclohexyloxy-phenyl)-4-trifluoromethyl-2H-pyridazin-3-one. The ketone was treated with phosphorous oxychloride (21.8 mmol, 2.0 mL) and heated at 90° C. for 1 hour with stirring. The reaction mixture was cooled to room temperature and the volatiles were removed under reduced pressure. The residue was dissolved in ethyl acetate (30 mL) and shaken with water (30 mL). The layers were separated and the organic layer was washed with saturated NaHCO3 (2×30 mL), brine (30 mL), dried (Na2SO4) filtered and concentrated under reduced pressure. The residue was purified on a 40 g SiO2 cartridge eluting with ethyl acetate/hexanes gradient to afford 3-butyl-6-chloro-4-(4-cyclohexyloxy-phenyl)-5-trifluoromethyl-pyridazine (0.65 g).

Provenance & Evidence