Carbon Dioxide → 3-Bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid

Temperature

-78 °C

To a mixture of 9.2 g of 2-(3-bromo-1H-pyrazol-1-yl)-3-chloropyridine and 80 ml of tetrahydrofuran was added dropwise 21.3 ml of a 2.0M lithium diisopropylamide solution in heptane/tetrahydrofuran/ethylbenzene at −78° C. The resulting mixture was stirred at −78° C. for 15 minutes, poured to a mixture of dry ice and 50 ml of tetrahydrofuran, and stirred for 1 hour with allowing it to rise to around room temperature. After water and diethyl ether were poured into the reaction mixture, the aqueous layer was adjusted to pH 10-12 by an addition of a 2N aqueous sodium hydroxide solution and layers were separated. The resulting aqueous layer was washed with diethyl ether two times, adjusted to around pH 3 by an addition of 2N hydrochloric acid, and extracted with methyl tert-butyl ether three times. The organic layers were combined, washed with an aqueous saturated sodium chloride solution, dried over magnesium sulfate, and concentrated under reduced pressure to obtain 7.96 g of 3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid of the formula:

1. stirringstirred for 1 hour
2. customto rise to around room temperature
3. customwere separated
4. washThe resulting aqueous layer was washed with diethyl ether two times
5. additionadjusted to around pH 3 by an addition of 2N hydrochloric acid
6. extractionextracted with methyl tert-butyl ether three times
7. washwashed with an aqueous saturated sodium chloride solution
8. dry with materialdried over magnesium sulfate
9. concentrationconcentrated under reduced pressure

ORD record

ord-e6d4273818ed4df19b72701d52b6116f

Source dataset

uspto-grants-2011_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07867949B2