Triethylamine → E-3-[2-{4-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl}ethenyl]quinuclidine

HRID 861434Notes

Reaction equation

HRID 861434 reaction equation
I[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]=[C:11]([CH3:13])[O:10][N:9]=2)=[CH:4][CH:3]=1.[CH:14]([CH:16]1[CH:21]2[CH2:22][CH2:23][N:18]([CH2:19][CH2:20]2)[CH2:17]1)=[CH2:15].C(N(CC)CC)C>CN(C)C=O.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Cu]I>[CH3:13][C:11]1[O:10][N:9]=[C:8]([C:5]2[CH:6]=[CH:7][C:2](/[CH:15]=[CH:14]/[CH:16]3[CH:21]4[CH2:22][CH2:23][N:18]([CH2:19][CH2:20]4)[CH2:17]3)=[CH:3][CH:4]=2)[N:12]=1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 53147561-Azabicyclo[2.2.2]octane, 3-ethenyl-HCID 19703103HCID 19703103, compound

Product 1

HCID 19703119E-3-[2-{4-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl}ethenyl]quinuclidineYield 10.2%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 3-(4-iodophenyl)-5-methyl-1,2,4-oxadiazole (1.43 g), 3-vinylquinuclidine (685 mg), bis(triphenylphosphine)palladium (II) chloride (175 mg), copper (I) iodide (90 mg) and triethylamine (5.0 ml) in dry dimethylformamide (10 ml) was stirred under argon at 100° C. for 5 hours. The dimethylformamide and triethylamine were removed by evaporation. The residue was treated with 2M aqueous sodium hydroxide solution (20 ml) and extracted with dichloromethane (3×20 ml). The organic extracts were washed with water (20 ml), dried (MgSO4) and evaporated. The residue was purified by flash column chromatography on silica gel using 5% methanol in dichloromethane containing 0.5% ammonia (density, 0.88 g/cm3) as eluent to give E-3-[2-{4-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl}ethenyl]quinuclidine (150 mg) as a solid, m.p. 93°-97° C.; NMR: 1.4(1H,m), 1.65(2H,m), 1.8(2H,m), 2.55(1H,m), 2.65(3H,s), 2.8(4H,m), 3.08(1H,m), 3.45(1H,m), 6.5(1H,d), 6.62(1H,d,d), 7.6(2H,d) and 7.82(2H,d).

Workup

  1. customThe dimethylformamide and triethylamine were removed by evaporation
  2. additionThe residue was treated with 2M aqueous sodium hydroxide solution (20 ml)
  3. extractionextracted with dichloromethane (3×20 ml)
  4. washThe organic extracts were washed with water (20 ml)
  5. dry with materialdried (MgSO4)
  6. customevaporated
  7. customThe residue was purified by flash column chromatography on silica gel using 5% methanol in dichloromethane containing 0.5% ammonia (density, 0.88 g/cm3) as eluent

Sources & evidence

ORD record
ord-df230d9705da40fd80e181dd8673c633
Source dataset
uspto-grants-1998_02
Patent number
US05714496

Reaction notes

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