Hydrochloric Acid → 2-(6-Chloropyridin-3-yl)acetonitrile

Temperature

0 °C

To a −78° C. solution of (6-chloropyridin-3-yl)methanol from Step 1 (7.5 g) and triethylamine (8.7 mL) in dichloromethane (250 mL) was slowly added methanesulphonyl chloride (4.5 mL). The reaction mixture was stirred at 0° C. for 1 hour. Then poured into ice and HCl (1N), adjusted pH at 4 with saturated aqueous disodium hydrogen phosphate and partitioned. The aqueous layer was extracted with dichloromethane (1×150 mL). The combined extracts were washed with brine, dried with magnesium sulfate and the solvent removed in vacuo. The residue was dissolved in DMF (100 mL) and sodium cyanide (2.8 g) was added. The reaction mixture was stirred at room temperature for 3 hours and poured into ice and water (100 mL). Extracted with ethyl acetate (2×100 mL). The combined extracts were washed with brine, dried with magnesium sulfate and the solvent removed in vacuo. The residue was purified by chromatography on SiO2 using ethyl acetate and hexanes (1:5 to 1:2) to yield the title compound.

1. customTo a −78° C.
2. custompartitioned
3. extractionThe aqueous layer was extracted with dichloromethane (1×150 mL)
4. washThe combined extracts were washed with brine
5. dry with materialdried with magnesium sulfate
6. customthe solvent removed in vacuo
7. dissolutionThe residue was dissolved in DMF (100 mL)
8. additionsodium cyanide (2.8 g) was added
9. stirringThe reaction mixture was stirred at room temperature for 3 hours
10. additionpoured into ice and water (100 mL)
11. extractionExtracted with ethyl acetate (2×100 mL)
12. washThe combined extracts were washed with brine
13. dry with materialdried with magnesium sulfate
14. customthe solvent removed in vacuo
15. customThe residue was purified by chromatography on SiO2

ORD record

ord-2e96d61ba37a4b4d8fc14884a57261f0

Source dataset

uspto-grants-2010_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07687524B2