Hydrochloric Acid → HCID 89875556, compound

Temperature

70 °C

To a mixture of zinc powder (2.29 g, 0.035 mol) and triglyme (17.5 mL) was added TMSBr (0.45 mL, 0.004 mol) under nitrogen, and the mixture was stirred at 70° C. for 1.5 h. After the reaction mixture was cooled to room temperature, ethyl bromodifluoroacetate (5.41 mL, 0.042 mol) was added while maintaining the internal temperature at 22 to 27° C., and the mixture was stirred at 20° C. for 30 min and then cooled to 0° C. After addition of a solution of isopropyl 5-bromopyrazine-2-carboxylate (II, 4.48 g, 0.017 mol) in DMA (51 mL) to the reaction mixture, the resulting mixture was warmed to 20° C. Copper bromide (CuBr, 5.02 g, 0.035 mol) was added in fifth portions over 1 h followed by stirring the mixture for 30 min. The resulting mixture was transferred into a pre-cooled (ice bath) mixture of an aqueous sodium chloride solution (6.3%, 55.5 g), concentrated hydrochloric acid (14.7 mL) and toluene (70 mL), and the resulting mixture was vigorously stirred. After phase separation, the organic layer was washed twice with an aqueous sodium chloride solution (5.7%, 35 g and 2.9%, 35 g) to afford 74.2 g of a toluene solution of isopropyl 5-(2-ethoxy-1,1-difluoro-2-oxoethyl)pyrazine-2-carboxylate (III).

1. temperatureAfter the reaction mixture was cooled to room temperature
2. temperaturewhile maintaining the internal temperature at 22 to 27° C.
3. stirringthe mixture was stirred at 20° C. for 30 min
4. temperaturecooled to 0° C
5. temperaturethe resulting mixture was warmed to 20° C
6. stirringby stirring the mixture for 30 min
7. temperaturea pre-cooled
8. stirringthe resulting mixture was vigorously stirred
9. customAfter phase separation
10. washthe organic layer was washed twice with an aqueous sodium chloride solution (5.7%, 35 g and 2.9%, 35 g)

ORD record

ord-07e87f1ae3454e4ba34999cd6ce47fe6

Source dataset

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09227942B2