Reaction #5072

Reaction equation

1-azabicyclo[2.2.1]heptan-3-one hydrochloride

benzophenone

lithium bis(trimethylsilyl)amide

→

title compound

2-(Diphenylhydroxymethyl)-1 -azabicyclo[2.2.1]heptan-3-one

Solvents

THF

Conditions

Workup

1. 1
   Temperatureto warm to room temperature
2. 2
   workup.STIRRINGstirred for 48 h
3. 3
   workup.ADDITIONThe mixture was poured onto water
4. 4
   Extractionextracted with dichloromethane (×4)
5. 5
   DryingThe combined extracts were dried (Na2SO4)
6. 6
   Otherevaporated in vacuo
7. 7
   Otherthe residue was purified by chromatography on silica using
8. 8
   Washa gradient elution of 10-30% ethyl acetate in dichloromethane

Procedure

To a stirred mixture of 1-azabicyclo[2.2.1]heptan-3-one hydrochloride (1.06 g) and benzophenone (1.82 g) in dry THF (5 ml) at -78° C. under argon was added a solution of lithium bis(trimethylsilyl)amide (18 ml, 1.0M in THF). The solution was stirred at -78° C. for 1 h, allowed to warm to room temperature and stirred for 48 h. The mixture was poured onto water and extracted with dichloromethane (×4). The combined extracts were dried (Na2SO4), evaporated in vacuo, and the residue was purified by chromatography on silica using a gradient elution of 10-30% ethyl acetate in dichloromethane to afford the title compound as a white solid:

Source