2-(6-Chloropyridin-3-yl)acetonitrile → HCID 86594352, compound

Temperature

-78 °C

KHMDS (30.9 mL of a 1 mmol mL−1 solution in THF, 30.9 mmol) was added to a stirred solution of (6-chloropyridin-3-yl)acetonitrile (4.40 g, 28.9 mmol) in anhydrous THF-HMPA (3:1, 72 mL) at −78° C. After 30 min, iodomethylcyclopentane (1.46 g, 6.9 mmol) was added. The solution was stirred at −78° C. for 4.5 h, before being allowed to warm to 20° C. over 16 h. The reaction mixture was carefully quenched with saturated aqueous NH4Cl (20 mL), then H2O (100 mL) was added. The mixture was extracted with EtOAc (3×50 mL), then the extracts were dried (Na2SO4). Filtration, solvent evaporation, and column chromatography (n-C6H14-EtOAc) furnished 2-(6-chloropyridin-3-yl)-3-cyclopentylpropionitrile: m/z (ES+)=235.1 [M+H]+. Step 2: This compound (2.30 g, 9.8 mmol) was heated with 50% aqueous H2SO4 (10 mL) at 130° C. for 2 h with stirring. The mixture was allowed to cool down to 20° C. over 16 h, before being neutralised with saturated aqueous Na2CO3 and extracted with CHCl3. The organic extracts were dried (Na2SO4), before being filtered and concentrated to give the title compound: m/z (ES+)=254.2 [M+H]+.

1. temperatureto warm to 20° C. over 16 h
2. customThe reaction mixture was carefully quenched with saturated aqueous NH4Cl (20 mL)
3. additionH2O (100 mL) was added
4. extractionThe mixture was extracted with EtOAc (3×50 mL)
5. dry with materialthe extracts were dried (Na2SO4)
6. filtrationFiltration, solvent evaporation, and column chromatography (n-C6H14-EtOAc)

ORD record

ord-751fd2419e8d4ddd9b85a876ced142f6

Source dataset

uspto-grants-2007_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07262196B2