Reacción #1141

Ecuación de reacción

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

Rendimiento 81.1%

Disolventes

toluene

Condiciones de reacción

Tratamiento posterior

1. 1
   Otrowere removed by distillation
2. 2
   workup.ADDITIONwater (10 mL) and ethyl acetate (20 mL) were added
3. 3
   OtroThe organic phase was separated
4. 4
   Extracciónthe aqueous layer extracted with ethyl acetate (2×20 mL)
5. 5
   Lavadothe combined organic extracts were washed with brine (10 mL)
6. 6
   Secadodried (MgSO4)
7. 7
   Concentraciónconcentrated in vacuo
8. 8
   OtroThe crude product was purified by silica gel column chromatography with ethyl acetate as eluant

Procedimiento

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).

Fuente