Dimethylformamide → HCID 69430458, compound

HRID 1295513Notes

Reaction equation

HRID 1295513 reaction equation
[CH2:1]([N:8]1[CH2:14][CH:13]2[C:15]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20](Br)[CH:19]=3)([O:16][CH3:17])[CH:10]([CH2:11][CH2:12]2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:25][N:26](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[CH2:14][CH:13]2[C:15]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([C:25]#[N:26])[CH:19]=3)([O:16][CH3:17])[CH:10]([CH2:11][CH2:12]2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 69428465HCID 69428465, compound

Product 1

HCID 69430458HCID 69430458, compound

Reagents, catalysts & solvents 2

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

Conditions

Temperature
85 °C

Procedure

3-Benzyl-8-(3-bromo-phenyl)-8-methoxy-3-aza-bicyclo[3.2.1]octane (2.17 g, 5.62 mmol) and zinc cyanide (0.99 g, 8.43 mmol) were combined in DMF (30 ml), degassed (evac./N2 purge 3×) then charged with tetrakis(triphenylphosphine) palladium (0) (3.24 g, 2.81 mmol). The resulting reaction mixture was heated to 85° C. in an oil bath for 5 h. Upon cooling to room temperature, the reaction mixture was filtered through a Celite pad and rinsed with EtOAc. The filtrate was extracted with 1 N HCl (2×50 ml) then neutralized to pH 8 with 1 N NaOH and saturated aqueous NaHCO3, causing an emulsion to form. The product was extracted with EtOAc (3×100 ml), washed with saturated aqueous NaCl solution (2×100 ml), dried over Na2SO4, filtered, and concentrated. The resulting crude product was dissolved in ether (100 ml) then washed with 50% saturated aqueous NaCl solution (4×100 ml), dried over Na2SO4, filtered and concentrated to a yellow oil (1.40 g, 75%). (TLC 20% EtOAc/hexanes Rf 0.40); 1H NMR (400 MHz, CDCl3) δ 7.69 (m, 2H), 7.56 (d, J=7.9 Hz, 1H), 7.45 (t, J=7.9 Hz, 1H), 7.36–7.20 (m, 5H), 3.58 (br s, 2H), 2.82 (s, 3H), 2.75 (d, J=10.3 Hz, 2H), 2.54 (br d, J=10.3 Hz, 2H), 2.43 (br s, 2H), 1.83 (d, J=8.1 Hz, 2H), 1.33 (m, 2H); APCI MS m/z 333.2 (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
  7. extractionThe filtrate was extracted with 1 N HCl (2×50 ml)
  8. customto form
  9. extractionThe product was extracted with EtOAc (3×100 ml)
  10. washwashed with saturated aqueous NaCl solution (2×100 ml)
  11. dry with materialdried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated
  14. dissolutionThe resulting crude product was dissolved in ether (100 ml)
  15. washthen washed with 50% saturated aqueous NaCl solution (4×100 ml)
  16. dry with materialdried over Na2SO4
  17. filtrationfiltered
  18. concentrationconcentrated to a yellow oil (1.40 g, 75%)

Sources & evidence

ORD record
ord-5eb1a2dbf01f427d8a43ab19f2687328
Source dataset
uspto-grants-2007_07
Patent number
US07241887B2

Reaction notes

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