4-(2-Oxiranylmethoxy)benzenecarbonitrile → 4-{3-[(3-Benzyl-3-azabicyclo[3.2.1]oct-8-yl)(methyl)amino]-2-hydroxypropoxy}benzonitrile

Participants

Reaction Conditions

Reaction Steps

To a solution of 3-benzyl-N-methyl-3-azabicyclo[3.2.1]octan-8-amine (Preparation B; 3.72 g, 16.1 mmol) in dichloromethane (80 mL) at 25° C. under nitrogen was added trimethylaluminum (8.05 mL of 2.0 M in hexane, 16.1 mmol). After stirring at 25° C. for 30 min, 4-(2-oxiranyl-methoxy)benzonitrile (see step (i) above; 2.83 g, 16.1 mmol) was added in one portion, and the mixture was stirred overnight. The mixture was quenched with 6 N NaOH (13.5 mL) and stirred 1 h. Water (100 mL) was added, and the aqueous layer was extracted with dichloromethane (3×100 mL). The combined organic extracts were dried (Na2SO4), filtered and concentrated in vacuo to afford an oil. The residue was chromatographed on silica gel, eluting with dichloromethane:methanol (98:2), to afford 4.30 g (66%) of the sub-title compound as a colorless oil.

Provenance & Evidence