Реакция #1138

Уравнение реакции

5-bromo-3-(1-tert-butyloxycarbonyl-2-pyrrolidinyl)pyridine

triphenylphosphine

potassium carbonate

2-methyl-3-butyn-2-ol

→

5-(2-hydroxy-2-methyl-3-butynyl)-3-(1-tert-butyloxycarbonyl-2-pyrrolidinyl)pyridine

Выход 76.4%

Растворители

DME

water

Water

ethyl acetate

Условия реакции

Обработка

1. 1
   Температураthe reaction flask was heated at 80° C. for 18 h
2. 2
   Фильтрацияthis was filtered through celite
3. 3
   ДругоеThe organic phase was separated
4. 4
   Экстракцияthe aqueous layer extracted with ethyl acetate (3×20 mL)
5. 5
   Промывкаthe combined ethyl acetate extracts were washed with brine (20 mL)
6. 6
   Сушкаdried (MgSO4)
7. 7
   Концентрированиеconcentrated in vacuo
8. 8
   ДругоеThe crude product was purified by silica gel column chromatography with ethyl acetate:hexane (1:3 to 1:1) as eluants

Методика

A mixture of 5-bromo-3-(1-tert-butyloxycarbonyl-2-pyrrolidinyl)pyridine (1 g, 3.06 mmol), 10% palladium on charcoal (80 mg, 0.077 mmol), copper(I)iodide (58 mg, 0.30 mmol), triphenylphosphine (80 mg, 0.30 mmol) and potassium carbonate (1.06 g, 7.65 mmol) in DME (5 mL) and water (5 mL) was stirred at 25° C. After 0.75 h 2-methyl-3-butyn-2-ol (0.74 mL, 7.65 mmol) was added and the reaction flask was heated at 80° C. for 18 h. Water (30 mL) and ethyl acetate (30 mL) were added to the cooled mixture and this was filtered through celite. The organic phase was separated and the aqueous layer extracted with ethyl acetate (3×20 mL) and the combined ethyl acetate extracts were washed with brine (20 mL), dried (MgSO4) and concentrated in vacuo. The crude product was purified by silica gel column chromatography with ethyl acetate:hexane (1:3 to 1:1) as eluants to afford 5-(2-hydroxy-2-methyl-3-butynyl)-3-(1-tert-butyloxycarbonyl-2-pyrrolidinyl)pyridine as an oil (772 mg, 76%). LRMS (EI) m/e 231 (M+ +H --CO2 and isobutylene), 230 (M+ --CO2 and isobutylene), 229 (M+ --CO2 tBu); 1H NMR (CDCl3, 300 MHz): δ 8.56 (b-s, 1H), 8.37 (b-d, J=1.5 Hz, 1H), 7.53 (m, 1H), 4.93 (b-m, 0.5H), 4.76 (b-m, 0.5H), 3.5-3.7 (b-m, 2H), 2.36 (m, 1H), 1.75-2.0 (b-m, 3H), 1.72 (b-s, 1H), 1.63 (s, 6H), 1.45 (b-s, 3H), 1.21 (b-s, 6H).

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