Nitrogen → Ammonium Hydroxide

Participants

Reaction Steps

To a solution of 4-[4-(3-benzyl-3,8-diazabicyclo[3.2.1]oct-8-yl)-1-(3,4-dimethoxyphenoxy)butyl]benzonitrile (9.2 g, 15.7 mmol; from step (d) above) in MeOH (1000 mL) was added 10% Pd/C (2.8 g) under a blanket of N2. The resulting solution was purged with H2 then stirred under a H2 atmosphere for 2 h. The solution was filtered through Celite® and the filtrate concentrated in vacuo to give a crushable foam. Flash chromatography on silica gel eluting first with CH2Cl2:MeOH:concentrated NH4OH (188:10:2 to 177:20:3 gradient) then a second flash chromatography with CHCl3:MeOH:AcOH (90:10:1 to 85:10:5 to 50:45:5 gradient) gave the AcOH salt of the title compound. The AcOH salt was neutralized with aqueous NaHCO3 and extracted with CH2Cl2 (3×). The combined organics were dried (Na2SO4), filtered and concentrated in vacuo to afford 3.2 g (48%) of the title compound.

Provenance & Evidence