Dimethylformamide → 4-[6-Butyl-5-(3-cyano-4-cyclohexyloxy-phenyl)-pyridazin-3-yloxy]-piperidine-1-carboxylic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

4-[5-(3-Bromo-4-cyclohexyloxy-phenyl)-6-butyl-pyridazin-3-yloxy]-piperidine-1-carboxylic acid tert-butyl ester (Example 65, 0.44 mmol, 0.26 g), Zinc cyanide (0.44 mmol, 0.052 g) in DMF (5.0 mL), water (0.05 mL) were degassed with nitrogen for 10 min then Pd2dba3 (0.022 mmol, 0.02 g), dppf (0.053 mmol, 0.029 g) was added and then degassed for 10 more min. The reaction mixture was heated at 120° C. for 36 h under nitrogen. Cooled, water was added extracted with ethyl acetate. The organic layer was washed with water, brine, dried (Na2SO4) filtered and concentrated under reduced pressure. The product was purified by column chromatography using 20% ethyl acetate in hexanes to get 4-[6-butyl-5-(3-cyano-4-cyclohexyloxy-phenyl)-pyridazin-3-yloxy]-piperidine-1-carboxylic acid tert-butyl ester (0.17 g).

Provenance & Evidence