Dimethylformamide → HCID 69431388, compound

HRID 1295509Notes

Reaction equation

HRID 1295509 reaction equation
[CH2:1]([N:8]1[CH2:14][CH:13]2[C:15]([C:17]3[CH:22]=[CH:21][CH:20]=[C:19](Br)[CH:18]=3)([OH:16])[CH:10]([CH2:11][CH2:12]2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:24][N:25](C=O)C>[C-]#N.[Zn+2].[C-]#N>[CH2:1]([N:8]1[CH2:14][CH:13]2[C:15]([C:17]3[CH:18]=[C:19]([CH:20]=[CH:21][CH:22]=3)[C:24]#[N:25])([OH:16])[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

4

Reactant 2

HCID 6228DimethylformamideHCID 694278793-Benzyl-8-(3-bromo-phenyl)-3-aza-bicyclo[3.2.1]octan-8-ol

Product 1

HCID 69431388HCID 69431388, compound

Reagents, catalysts & solvents 1

HCID 11186Zinc cyanide (Zn(CN)2)Catalyst

Procedure

3-Benzyl-8-(3-bromo-phenyl)-3-aza-bicyclo[3.2.1]octan-8-ol (2.17 g, 5.83 mmol) and zinc cyanide (1.03 g, 8.75 mmol) were combined in DMF (30 mL), degassed (evac/N2 purge 3×) then charged with tetrakistriphenylphosphine palladium (0) (3.37 g, 2.91 mmol). The resulting reaction mixture was heated to 85 □ C. in an oil bath for 5 h (or until complete by TLC). After 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 solution, 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), washed with 50% saturated aqueous NaCl solution (4×100 mL), dried over Na2SO4, filtered and concentrated to a brown oil (1.86 g, 100%). (TLC 40% EtOAc/Hexanes Rf 0.42); 1H NMR (400 MHz, CDCl3) δ 7.76–7.72 (m, 2H), 7.55 (br d, J=7.9 Hz, 1H), 7.45 (t, J=7.9 Hz, 1H), 7.36–7.20 (m, 5H), 3.59 (br s, 2H), 2.84 (d, J=10.8 Hz, 2H), 2.61 (br d, J=10.8 Hz, 2H), 2.36 (br, s, 2H), 1.83 (d, J=7.5 Hz, 2H), 1.35 (m, 2H); APCI MS m/z 319.2 (M+1)+.

Workup

  1. customdegassed
  2. custom(evac/N2 purge 3×)
  3. customThe resulting reaction mixture
  4. temperaturewas heated to 85 □ C
  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. washwashed with 50% saturated aqueous NaCl solution (4×100 mL)
  16. dry with materialdried over Na2SO4
  17. filtrationfiltered
  18. concentrationconcentrated to a brown oil (1.86 g, 100%)

Sources & evidence

ORD record
ord-ad5023adf24a4cbd92d89b30708712d1
Source dataset
uspto-grants-2007_07
Patent number
US07241887B2

Reaction notes

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