Triethylamine → 3-[2-(6-Butoxy-3-pyridyl)ethynyl]quinuclidin-3-ol

HRID 2742

Reaction equation

HRID 2742 reaction equation
[C:1]([C:3]1([OH:11])[CH:8]2[CH2:9][CH2:10][N:5]([CH2:6][CH2:7]2)[CH2:4]1)#[CH:2].Br[C:13]1[CH:14]=[CH:15][C:16]([O:19][CH2:20][CH2:21][CH2:22][CH3:23])=[N:17][CH:18]=1.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>[CH2:20]([O:19][C:16]1[N:17]=[CH:18][C:13]([C:2]#[C:1][C:3]2([OH:11])[CH:8]3[CH2:9][CH2:10][N:5]([CH2:6][CH2:7]3)[CH2:4]2)=[CH:14][CH:15]=1)[CH2:21][CH2:22][CH3:23]

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 36135173-Ethynyl-1-azabicyclo[2.2.2]octan-3-olHCID 189362685-Bromo-2-butoxypyridine

Product 1

HCID 99482783-[2-(6-Butoxy-3-pyridyl)ethynyl]quinuclidin-3-olYield 25.2%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
90 °C

Procedure

A stirred mixture of 3-ethynyl-3-hydroxyquinuclidine (600 mg), 5-bromo-2-n-butoxypyridine (920 mg), bis-(triphenylphosphine)-palladium (II) chloride (140 mg), copper (I) iodide (70 mg) and dry triethylamine (10 ml) in dry dimethylformamide (20 ml) was heated at 90° C. under an atmosphere of argon for 6 hours. The reaction mixture was cooled and the dimethylformamide and triethylamine were removed by evaporation. The residue was treated with 2M aqueous sodium hydroxide solution (20 ml) and the resulting mixture extracted with dichloromethane (3×20 ml). The organic extracts were combined, dried (MgSO4) and evaporated to give a brown residue which was crystallised from acetonitrile to yield 3-[2-(6-butoxy-3-pyridyl)ethynyl]quinuclidin-3-ol (300 mg) as a solid, m.p. 149°-151° C.; microanalysis, found: C, 71.3; H, 7.9; N, 8.9%; C18H24N2O2 0.1H 2O requires: C, 71.47; H, 8.08; N, 9.26%; NMR (DHSOd6): 0.9-1.0(3H, t), 1.2-1.35(1H, m), 1.35-1.5(2H, m), 1.5-1.65(1H, m), 1.65-1.75(2H, m), 1.75-2.0(3H, m), 2.6-2.75(4H, t), 2.8-2.85(1H, d), 3.02-3.17(1H, d), 4.2-4.3(2H, t), 5.55(1H, s), 6.75-6.83(1H, d), 7.65-7.72(1H, d) and 8.2(1H, s); m/Z 301 (M+H).

Workup

  1. temperatureThe reaction mixture was cooled
  2. customthe dimethylformamide and triethylamine were removed by evaporation
  3. additionThe residue was treated with 2M aqueous sodium hydroxide solution (20 ml)
  4. extractionthe resulting mixture extracted with dichloromethane (3×20 ml)
  5. dry with materialdried (MgSO4)
  6. customevaporated
  7. customto give a brown residue which
  8. customwas crystallised from acetonitrile

Sources & evidence

ORD record
ord-c6c10cd15dfc4d01b84ec18ab3764f16
Source dataset
uspto-grants-1998_03
Patent number
US05731323

Linked notes

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