Réaction #2838

Équation de réaction

3-ethynyl-3-hydroxyquinuclidine

5-bromo-2-n-butoxypyridine

triethylamine

→

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

Rendement 25.2%

Solvants

dimethylformamide

Conditions de réaction

Traitement

1. 1
   TempératureThe reaction mixture was cooled
2. 2
   Autrethe dimethylformamide and triethylamine were removed by evaporation
3. 3
   workup.ADDITIONThe residue was treated with 2M aqueous sodium hydroxide solution (20 ml)
4. 4
   Extractionthe resulting mixture extracted with dichloromethane (3×20 ml)
5. 5
   Séchagedried (MgSO4)
6. 6
   Autreevaporated
7. 7
   Autreto give a brown residue which
8. 8
   Autrewas crystallised from acetonitrile

Mode opératoire

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).

Source