Реакция #2838

Уравнение реакции

3-ethynyl-3-hydroxyquinuclidine

5-bromo-2-n-butoxypyridine

triethylamine

→

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

Выход 25.2%

Растворители

dimethylformamide

Условия реакции

Обработка

1. 1
   ТемператураThe reaction mixture was cooled
2. 2
   Другоеthe dimethylformamide and triethylamine were removed by evaporation
3. 3
   workup.ADDITIONThe residue was treated with 2M aqueous sodium hydroxide solution (20 ml)
4. 4
   Экстракцияthe resulting mixture extracted with dichloromethane (3×20 ml)
5. 5
   Сушкаdried (MgSO4)
6. 6
   Другоеevaporated
7. 7
   Другоеto give a brown residue which
8. 8
   Другоеwas crystallised from acetonitrile

Методика

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).

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