Reaktion #2838

Reaktionsgleichung

3-ethynyl-3-hydroxyquinuclidine

5-bromo-2-n-butoxypyridine

triethylamine

→

3-[2-(6-butoxy-3-pyridyl)ethynyl]quinuclidin-3-ol

Ausbeute 25.2%

Lösungsmittel

dimethylformamide

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturThe reaction mixture was cooled
2. 2
   Sonstigethe dimethylformamide and triethylamine were removed by evaporation
3. 3
   workup.ADDITIONThe residue was treated with 2M aqueous sodium hydroxide solution (20 ml)
4. 4
   Extraktionthe resulting mixture extracted with dichloromethane (3×20 ml)
5. 5
   Trocknendried (MgSO4)
6. 6
   Sonstigeevaporated
7. 7
   Sonstigeto give a brown residue which
8. 8
   Sonstigewas crystallised from acetonitrile

Vorschrift

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).

Quelle