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

HRID 225390Notes

Reaction equation

HRID 225390 reaction equation
[CH2:1]([N:8]1[CH2:15][CH2:14][C:13]2([C:17]3[CH:18]=[C:19](OS(C(F)(F)F)(=O)=O)[CH:20]=[CH:21][CH:22]=3)[CH2:16][CH:9]1[CH2:10][CH2:11][CH2:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:31][N:32](C=O)C>[C-]#N.[Zn+2].[C-]#N.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH2:1]([N:8]1[CH2:15][CH2:14][C:13]2([C:17]3[CH:18]=[C:19]([CH:20]=[CH:21][CH:22]=3)[C:31]#[N:32])[CH2:16][CH:9]1[CH2:10][CH2:11][CH2:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 86594615Trifluoro-methanesulfonic acid 3-(2-benzyl-2-aza-bicyclo[3.3.1]non-5-yl)-phenyl ester

Product 1

HCID 220645903-(2-Benzyl-2-aza-bicyclo[3.3.1]non-5-yl)-benzonitrileYield 54%

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalyst

Conditions

Temperature
85 °C

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)+.

Workup

  1. customdegassed
  2. custom(evac./N2 purge 3×)
  3. customThe resulting reaction mixture
  4. temperatureUpon cooling to room temperature
  5. filtrationthe reaction mixture was filtered through a Celite pad
  6. washrinsed with EtOAc (200 ml)
  7. washThe filtrate was washed with water and saturated aqueous NaCl solution (1×200 ml each)
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customchromatographed on silica gel eluting with 50% EtOAc/hexanes

Sources & evidence

ORD record
ord-9d4a45cfd68d4a80872386035f504335
Source dataset
uspto-grants-2009_07
Patent number
USRE040838E1

Reaction notes

Loading…