2-Chloronicotinoyl chloride → (2-Chloropyridin-3-yl)(cyclopropyl)methanone

温度

-78 °C

A mixture of cyclopropyltributyltin (0.5 g, 1.51 mmol) in 3 mL of THF was cooled to -78° C. and then n-butyllithium (0.604 mL, 2.5M in hexanes, 1.51 mmol) was added. The mixture was stirred at 0° C. for 0.5 hours. A mixture of copper(I) iodide (0.142 g, 0.75 mmol) in THF was cooled to -40° C. and the mixture containing the cyclopropyltributyltin was added. The mixture was stirred for 45 minutes and then 2-chloronicotinic acid chloride (0.265 g, 1.51 mmol) was added dropwise. The mixture was stirred at -40° C. for 1.5 hours and allowed to warm to room temperature. The mixture was quenched with water, diluted with methylene chloride, filtered and the aqueous layer was extracted with methylene chloride (2×30 mL). The combined organic layers were dried (Na2SO4) and concentrated. The residue was purified on silica gel by flash chromatography eluting with hexanes/ethyl acetate (85:15) to give 2-chloro-3-pyridyl cyclopropyl ketone (0.15 g, 0.83 mmol) as an oil.

1. temperaturewas cooled to -40° C.
2. additionwas added
3. stirringThe mixture was stirred for 45 minutes
4. stirringThe mixture was stirred at -40° C. for 1.5 hours
5. temperatureto warm to room temperature
6. customThe mixture was quenched with water
7. additiondiluted with methylene chloride
8. filtrationfiltered
9. extractionthe aqueous layer was extracted with methylene chloride (2×30 mL)
10. dry with materialThe combined organic layers were dried (Na2SO4)
11. concentrationconcentrated
12. customThe residue was purified on silica gel by flash chromatography
13. washeluting with hexanes/ethyl acetate (85:15)

ORDレコード

ord-e086ee4a67aa4eb2a8cfa095ccbfb495

出典データセット

uspto-grants-1997_11

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US05688795