Water → 3-[5-(4-Benzyloxy-phenyl)-6-butyl-pyridazin-3-yloxymethyl]-pyrrolidine-1-carboxylic acid tert-butyl ester

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Reaction Steps

To a stirred solution of 3-hydroxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (1.5 mmol, 302 mg) in THF (4.0 mL) at 0° C., NaH (60% dispersion in mineral oil, 1.5 mmol, 60 mg) was added and stirring continued for 10 min at room temperature, then 4-(4-benzyloxy-phenyl)-3-butyl-6-chloro-pyridazine (Example 1, 1.0 mmol, 352 mg) was added. The resulting mixture was stirred at 50° C. for 1 hour, poured into water and extracted with ethyl acetate. The organic layers were combined and concentrated under reduced pressure. The product was purified by column chromatography using 50% ethyl acetate in hexanes to give 3-[5-(4-benzyloxy-phenyl)-6-butyl-pyridazin-3-yloxymethyl]-pyrrolidine-1-carboxylic acid tert-butyl ester, which was dissolved in dichloromethane (1.0 mL), added 4.0 M HCl in dioxane (1.0 mL) and stirred at room temperature for 1 hour. Solvents were evaporated to provide 4-(4-benzyloxy-phenyl)-3-butyl-6-(pyrrolidin-3-ylmethoxy)-pyridazine dihydrochloride.

Provenance & Evidence