Reaction #6948

Reaction equation

methyl iodide

3-oxo-3-pyridin-3-yl-propionitrile

CS2

NH4Cl

1-bromo-butan-2-one

→

desired product

Yield 32.1%

1-(4-Methyl-5-methylsulfanyl-3-pyridin-3-yl-thiophen-2-yl)-propan-1-one

Yield 32.1%

Solvents

DMF

Conditions

Workup

1. 1
   workup.STIRRINGThe reaction was stirred for another 30 minutes
2. 2
   workup.STIRRINGThe resulting mixture was stirred for another 30 minutes
3. 3
   Temperaturethen warmed to ambient temperature
4. 4
   ExtractionThe solution was extracted with ethyl acetate (200 mL×3)
5. 5
   Dryingthe combined organic layers were dried over Na2SO4
6. 6
   Concentrationthen concentrated in vacuo
7. 7
   OtherPurification by chromatography (Silica Gel, 3:1 hexanes:ethyl acetate)

Procedure

To a solution of 3-oxo-3-pyridin-3-yl-propionitrile (11.9 mmol) in DMF (100 mL) was added CS2 (0.90 ml, 15.0 mmol) at 0° C. The reaction was stirred at 0° C. for 45 minutes under nitrogen then 1-bromo-butan-2-one (1.79 g, 11.8 mmol) was added via a syringe at 0° C. The reaction was stirred for another 30 minutes then methyl iodide (1.69 g, 11.8 mmol) was added via syringe at 0° C. The resulting mixture was stirred for another 30 minutes then warmed to ambient temperature and poured into saturated aqueous NH4Cl solution (300 mL). The solution was extracted with ethyl acetate (200 mL×3) and the combined organic layers were dried over Na2SO4 then concentrated in vacuo. Purification by chromatography (Silica Gel, 3:1 hexanes:ethyl acetate) afforded 1.05 g desired product. 1H NMR (CDCl3): δ 8.8 (d, 1H), 8.6 (s, 1H), 7.8 (d, 1H), 7.5 (dd, 1H), 2.8 (s, 3H), 2.3 (q, 2H), 1.0 (t, 3H).

Source