Reaction #1141

Reaction equation

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

Yield 81.1%

Solvents

toluene

Conditions

Workup

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

Procedure

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).

Source