Hydrochloric Acid → 4-[3-(3,8-Diazabicyclo[3.2.1]oct-8-yl)-2-hydroxypropoxy]benzonitrile
Reaction equation
C([N:8]1[CH2:14][CH:13]2[N:15]([CH2:16][CH:17]([OH:28])[CH2:18][O:19][C:20]3[CH:27]=[CH:26][C:23]([C:24]#[N:25])=[CH:22][CH:21]=3)[CH:10]([CH2:11][CH2:12]2)[CH2:9]1)C1C=CC=CC=1.Cl>C(#N)C>[CH:13]12[N:15]([CH2:16][CH:17]([OH:28])[CH2:18][O:19][C:20]3[CH:21]=[CH:22][C:23]([C:24]#[N:25])=[CH:26][CH:27]=3)[CH:10]([CH2:11][CH2:12]1)[CH2:9][NH:8][CH2:14]2Participants
4
Procedure
To a cold solution of 4-[3-(3-benzyl-3,8-diazabicyclo[3.2.1.]oct-8-yl)-2-hydroxypropoxy]benzonitrile (5.74 g, 15.2 mmol; from step (a) above) in acetonitrile (100 mL) there was added 12 M HCl (3.2 mL). The reaction mixture was stirred for 15 minutes, concentrated in vacuo and dried under high vacuum overnight. The resulting hydrochloride salt was added to a suspension of 10% Pd/C (700 mg) in methanol (500 mL). The reaction was then stirred under hydrogen (1 atmosphere of pressure) for 90 minutes. The mixture was filtered through Celite® and the filtrate concentrated in vacuo. The resulting residue was partitioned with saturated sodium bicarbonate (100 mL) and CH2Cl2 (150 mL). The organic layer was dried (Na2SO4), filtered and concentrated in vacuo to give the crude product. Flash chromatography on silica gel, eluting with CH2Cl2:CMA (4:1), gave 1.58 g (38%) of the sub-title compound.