Dimethyl Sulfoxide → (4-Chloro-3-difluoromethoxy-2-pyridyl)cyclopropylketone

Temperature

-78 °C

0.30 ml of oxalyl chloride was dissolved in 10 ml of anhydrous dichloromethane, and under cooling at −78° C., 0.27 ml of anhydrous dimethylsulfoxide in 3 ml of anhydrous dichloromethane solution was dropped thereto. The resulting mixture was stirred at −78° C. for 40 minutes, and thereafter, 0.62 g of (4-chloro-3-difluoromethyl-2-pyridyl)cyclopropylmethane-1-ol (IX) in 7 ml of anhydrous dichloromethane solution was dropped thereto. The resulting mixture was stirred at −78° C. for 30 minutes, and thereafter, the reaction temperature was elevated to −45° C. and the resulting mixture was stirred at the same temperature for 1 hour, and thereafter, 1.86 ml of triethylamine was dropped and the temperature of the resulting mixture was elevated to a room temperature. Water was added thereto and the resulting mixture was extracted with chloroform, and the resulting organic layer was washed with water and saturated salt water, and thereafter, dried over anhydrous sodium sulfate and the solvent was distilled off under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluent; chloroform:ethyl acetate=19:1) to obtain 0.53 g of (4-chloro-3-difloromethyl-2-pyridyl)cyclopropylketone (X).

1. stirringThe resulting mixture was stirred at −78° C. for 30 minutes
2. customwas elevated to −45° C.
3. stirringthe resulting mixture was stirred at the same temperature for 1 hour
4. customwas elevated to a room temperature
5. extractionthe resulting mixture was extracted with chloroform
6. washthe resulting organic layer was washed with water and saturated salt water
7. dry with materialdried over anhydrous sodium sulfate
8. distillationthe solvent was distilled off under reduced pressure
9. customThe resulting residue was purified by silica gel column chromatography (eluent; chloroform:ethyl acetate=19:1)

ORD record

ord-22aa6a3314e5469d96d70ab07f60d0f5

Source dataset

uspto-grants-2003_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06525066B2