A cooled solution of cyclopropanemethanol (1.8 g; 25 mmol) in THF (7 mL) was added to a stirred 0C dispersion of CDI (4.05 g; 25 mmol) in THF (15 mL), and the reaction mixture was stirred for 30 minutes. A fraction of this solution (3.75 mL; 4.35 mmol) was added to a dispersion of 4-[3-(3,7-diazabicyclo[3.3.1]non-3-yl)-2(S)-hydroxypropoxy)benzonitrile (2.25 g; 6.0 mmol; dihydrochloride salt; prepared from 3,7-diazabicyclo[3.3.1]nonane-3-carboxylic acid and 7-[(2S)-3-(4-cyanophenoxy)-2-hydroxypropyl]-1,1-dimethylethyl ester, analogously to the method described in Example G above) and K2CO3 (2.0 g; 14.5 mmol) in THF (10 mL). The reaction mixture was heated (85° C.) in a sealed steel vessel for 24 hours, was then concentrated, and the residue partitioned between DCM and water. The organic layer was collected, dried, concentrated and subjected to column chromatography (DCM:MeOH; 95:5) to give the title compound in a 29% yield.
