Реакция #1141

Уравнение реакции

5-(2-Hydroxy-2-methyl-3-butynyl)-3-(1-methyl-5-pyrrolidin-2-onyl)pyridine

sodium hydride

toluene acetone

→

5-ethynyl-3-(1-methyl-5-pyrrolidin-2-onyl)pyridine

Выход 81.1%

Растворители

toluene

Условия реакции

Обработка

1. 1
   Другоеwere removed by distillation
2. 2
   workup.ADDITIONwater (10 mL) and ethyl acetate (20 mL) were added
3. 3
   ДругоеThe organic phase was separated
4. 4
   Экстракцияthe aqueous layer extracted with ethyl acetate (2×20 mL)
5. 5
   Промывкаthe combined organic extracts were washed with brine (10 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 as eluant

Методика

5-(2-Hydroxy-2-methyl-3-butynyl)-3-(1-methyl-5-pyrrolidin-2-onyl)pyridine (200 mg, 0.77 mmol) was dissolved in toluene (20 mL) and catalytic sodium hydride (5 mg) was added. The solution was heated until several milliliters of toluene-acetone mixture were removed by distillation. The mixture was cooled to 25° C. and water (10 mL) and ethyl acetate (20 mL) were added. The organic phase was separated and the aqueous layer extracted with ethyl acetate (2×20 mL) and the combined organic extracts were washed with brine (10 mL), dried (MgSO4) and concentrated in vacuo. The crude product was purified by silica gel column chromatography with ethyl acetate as eluant to afford 5-ethynyl-3-(1-methyl-5-pyrrolidin-2-onyl)pyridine as a solid (125 mg, 81%). M.p. 83°-84° C.; 1H NMR (CDCl3, 300 MHz): δ 8.69 (d, J=2 Hz, 1H), 8.46 (d, J=2 Hz, 1H), 7.62 (t, J=2 Hz, 1H), 4.57 (dd, J=7, 6 Hz, 1H), 3.28 (s, 1H), 2.70 (s, 3H), 2.45-2.65 (m, 3H), 1.88 (m, 1H).

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