Triethylamine → 6,9-Dihydro-5H-6,9-methanocyclohepta[b]pyridine

HRID 272596Notes

Reaction equation

HRID 272596 reaction equation
[CH:1]1([CH2:6][C:7]2[C:8](OS(C(F)(F)F)(=O)=O)=[N:9][CH:10]=[CH:11][CH:12]=2)[CH2:5][CH:4]=[CH:3][CH2:2]1.C(N(CC)CC)C.C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:4]12[CH2:5][CH:1]([CH:2]=[CH:3]1)[CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[N:9][C:8]2=1

Participants

6

Reactant 3

HCID 8471Triethylamine2×HCID 812191,3-Bis(diphenylphosphino)propaneHCID 598378582-(Trifluoromethylsulfonyloxy)-3-(3-cyclopentenylmethyl)pyridine

Product 1

HCID 688081066,9-Dihydro-5H-6,9-methanocyclohepta[b]pyridineYield 77%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

Trifluoro-methanesulfonic acid 3-cyclopent-3-enylmethyl-pyridin-2-yl ester (3.1 g, 10.1 mmol) was stirred in DMF (20 mL) and degassed (3 N2/vacuum cycles) then treated under a N2 atmosphere with triethylamine (1.52 g, 15 mmol), 1,3-bis(diphenylphosphino)propane (334 mg, 0.80 mmol) and palladium acetate (72 mg, 0.32 mmol). After 20 min. the mixture was warmed to 100° C. under nitrogen for 18 h, at which time the reaction was deemed 90% complete. Additional triethylamine (1 mL, 7.2 mmol) was added and the mixture brought to 110° C. for 6 h at which time TLC analysis indicated complete consumption of starting material. The reaction mixture was cooled and poured into 50% saturated aqueous NaCl solution (75 mL) then extracted with EtOAc (4×30 mL). The combined organic layer was washed with H2O (2×50 mL), saturated aqueous NaHCO3 solution (50 mL), saturated aqueous NaCl solution (50 mL), dried over Na2SO4, filtered and concentrated to an oil, 2.3 g. Of this material 1.89 g was chromatographed on silica gel eluting with 20% EtOAc/hexanes to provide an oil (1.07 g, 77%). (TLC 20% EtOAc/hexanes Rf 0.21); 1H NMR (400 MHz, CDCl3) δ 8.10 (dd, J=4.9, 0.7 Hz, 1H), 7.18 (d, J=7.5 Hz, 1H), 6.92 (dd, J=7.5, 4.9 Hz, 1H), 6.21 (dd, J=5.5, 2.9 Hz, 1H), 5.73 (dd, J=5.5, 2.6 Hz, 1H), 3.43 (m, 1H), 2.86 (m, 2H), 2.40 (d, J=16.2 Hz, 1H), 2.21 (m, 1H), 1.80 (d, J=10.2 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 162.0, 145.0, 138.2, 138.0, 131.7, 130.1, 121.6, 47.3, 39.5, 37.9, 29.7; APCl MS m/z 158.1 (M)+.

Workup

  1. customdegassed (3 N2/vacuum cycles)
  2. customconsumption of starting material
  3. temperatureThe reaction mixture was cooled
  4. additionpoured into 50% saturated aqueous NaCl solution (75 mL)
  5. extractionthen extracted with EtOAc (4×30 mL)
  6. washThe combined organic layer was washed with H2O (2×50 mL), saturated aqueous NaHCO3 solution (50 mL), saturated aqueous NaCl solution (50 mL)
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated to an oil, 2.3 g
  10. customOf this material 1.89 g was chromatographed on silica gel eluting with 20% EtOAc/hexanes

Sources & evidence

ORD record
ord-66b34962b2014d9b91b1d83a94b41d45
Source dataset
uspto-grants-2008_11
Patent number
US07456177B2

Reaction notes

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