Reaction #312572

Reaction equation

Trifluoro-methanesulfonic acid 3-(2-benzyl-2-aza-bicyclo[3.3.1]non-5-yl)-phenyl ester

DMF

→

oil

Yield 54.0%

3-(2-Benzyl-2-aza-bicyclo[3.3.1]non-5-yl)-benzonitrile

Yield 54.0%

Conditions

Workup

1. 1
   Otherdegassed
2. 2
   Other(evac./N2 purge 3×)
3. 3
   OtherThe resulting reaction mixture
4. 4
   TemperatureUpon cooling to room temperature
5. 5
   Filtrationthe reaction mixture was filtered through a Celite pad
6. 6
   Washrinsed with EtOAc (200 ml)
7. 7
   WashThe filtrate was washed with water and saturated aqueous NaCl solution (1×200 ml each)
8. 8
   Dryingdried over Na2SO4
9. 9
   Filtrationfiltered
10. 10
    Concentrationconcentrated
11. 11
    Otherchromatographed on silica gel eluting with 50% EtOAc/hexanes

Procedure

Trifluoro-methanesulfonic acid 3-(2-benzyl-2-aza-bicyclo[3.3.1]non-5-yl)-phenyl ester (5.00 g, 11.4 mmol) and zinc cyanide (1.47 g, 12.5 mmol) were combined in DMF (110 ml), degassed (evac./N2 purge 3×) then charged with tetrakis(triphenylphosphine) palladium (0) (1.8 g, 1.60 mmol). The resulting reaction mixture was heated to 85° C. in an oil bath for 6 h. Upon cooling to room temperature, the reaction mixture was filtered through a Celite pad and rinsed with EtOAc (200 ml). The filtrate was washed with water and saturated aqueous NaCl solution (1×200 ml each), dried over Na2SO4, filtered, and concentrated and chromatographed on silica gel eluting with 50% EtOAc/hexanes to provide an oil (1.95 g, 54%). (TLC 50% EtOAc/hexanes Rf 0.28); 1H NMR (400 MHz, CDCl3) δ 7.49-7.52 (m, 2H), 7.45-7.48 (m, 3H), 7.35-7.39 (m, 2H), 7.10-7.14 (m, 1H), 7.00-7.02 (m, 1H), 3.98 (ABq, □AB=48.9 Hz, J=13.0 Hz, 2H), 3.31—3.33 (m, 1H), 3.16-3.21 (m, 2H), 2.21-2.25 (m, 2H), 1.95 2.07 (m, 4H), 1.76 1.80 (m, 2H), 1.41 1.59 (m, 2H); APCl MS m/z 317.2 (M+1)+.

Source