Chloroacetyl chloride → 2-chloro-N-(5-nitropyridin-2-yl)acetamide

温度

0 °C

2-Amino-5-nitropyridine (19) (4.0 g, 28.8 mmol) was dissolved in THF (300 mL). TEA (12.0 mL, 86.1 mmol) was added and the stirred mixture cooled to 0° C. Chloroacetyl chloride (7.0 mL, 87.9 mmol) was added dropwise. The stirred solution was allowed to warm to rt then stirred at this temperature for 1 hour. The mixture was heated at reflux for 1 hour. The solvent was evaporated in vacuo and the residue partitioned between DCM (100 mL) and saturated aqueous sodium bicarbonate solution (50 mL). The layers were separated and the organic phase washed with saturated brine solution (50 mL), then separated, dried over MgSO4, filtered and concentrated in vacuo. Approximately half the crude product was purified by column chromatography (Biotage SP1) eluting with isohexane→30% EtOAc-isohexane, combining the crude material with this purified product. The combined material was triturated with EtOAc-isohexane to provide the title compound as a brown solid (3.6 g, 58%); Rf: 0.45 (3:1 isohexane-EtOAc).

1. temperatureto warm to rt
2. temperatureThe mixture was heated
3. temperatureat reflux for 1 hour
4. customThe solvent was evaporated in vacuo
5. customthe residue partitioned between DCM (100 mL) and saturated aqueous sodium bicarbonate solution (50 mL)
6. customThe layers were separated
7. washthe organic phase washed with saturated brine solution (50 mL)
8. customseparated
9. dry with materialdried over MgSO4
10. filtrationfiltered
11. concentrationconcentrated in vacuo
12. customApproximately half the crude product was purified by column chromatography (Biotage SP1)
13. washeluting with isohexane→30% EtOAc-isohexane
14. customThe combined material was triturated with EtOAc-isohexane

ORDレコード

ord-3829d96597fd4fa58b39d4fcf2944881

出典データセット

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09433622B2