反应详情

A mixture of sodium cyanoborohydride (35.0 g, 0.557 mol) and zinc chloride (37.9 g, 0.278 mol) in methanol (500 mL) was added dropwise to a mechanically stirred mixture of 3-benzyl-3-azabicyclo[3.2.1]octan-8-one (Preparation A; 120 g, 0.557 mol) and methylamine hydrochloride (151 g, 2.23 mol) in methanol (1.0 L) at 25° C. under nitrogen. After 2.5 h of stirring, 6 N NaOH (90 mL) was added dropwise. The mixture was filtered through a pad of Celite®, washing with methanol (500 mL). The filtrate was concentrated in vacuo. Water (500 mL) was added, and the aqueous mixture was extracted with ethyl acetate (3×500 mL). The combined organic extracts were dried (Na2SO4), and concentrated in vacuo. The residue was chromatographed, eluting with methanol dichloromethane (1:10), to afford 63.0 g (49%) of the sub-title compound as a solid.

1. customPreparation A
2. customat 25° C.
3. filtrationThe mixture was filtered through a pad of Celite®
4. washwashing with methanol (500 mL)
5. concentrationThe filtrate was concentrated in vacuo
6. additionWater (500 mL) was added
7. extractionthe aqueous mixture was extracted with ethyl acetate (3×500 mL)
8. dry with materialThe combined organic extracts were dried (Na2SO4)
9. concentrationconcentrated in vacuo
10. customThe residue was chromatographed
11. washeluting with methanol dichloromethane (1:10)