101012-32-2

2-(2-Chloropyridin-3-yl)acetonitrile is a useful reagent in the preparation of spirocyclic oxindole analog(spiro[piperidine-?4,?3''-?pyrrolo[2,?3-?b]?pyridin]?-?2''(1''H)?-?one) with anti-tumor properties.

The general procedure for the synthesis of (2-chloropyridin-3-yl)acetonitrile from (1-yloxy-pyridin-3-yl)-acetonitrile is as follows: 1. under vigorous stirring, (1 -oxy-pyridin-3-yl)acetonitrile (7.5 g, 35.9 mmol) was slowly added to phosphoryl chloride (100 mL). 2. The reaction mixture was slowly heated to 80°C in 5°C increments over 1.5 hours. (Note: too rapid a heating rate may result in violent decomposition at about 70°C.) 3. Allow all solids to dissolve and continue heating to reflux for 3 hours. 4. When the reaction is complete, carefully remove the excess phosphorus trichloride and dispose of the residue in cold water. 5. The mixture was adjusted to alkaline by adding saturated sodium bicarbonate solution and subsequently extracted with ethyl acetate (3 x). 6. The organic extracts were combined, washed with brine, dried, filtered and concentrated. 7. Purify the residue by column chromatography with an elution gradient of pentane to 100% ether. 8. The second eluted compound from the column chromatography, the target product (2-chloropyridin-3-yl)acetonitrile (2.35 g, 42.9% yield), was collected as a light brown solid.

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