Reaktion #339097

Reaktionsgleichung

sodium hydroxide

lithium diisopropylamide

dry ice

2-(3-bromo-1H-pyrazol-1-yl)-3-chloropyridine

→

3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid

Lösungsmittel

diethyl ether

water

heptane tetrahydrofuran ethylbenzene

tetrahydrofuran

tetrahydrofuran

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGstirred for 1 hour
2. 2
   Sonstigeto rise to around room temperature
3. 3
   Sonstigewere separated
4. 4
   WaschenThe resulting aqueous layer was washed with diethyl ether two times
5. 5
   workup.ADDITIONadjusted to around pH 3 by an addition of 2N hydrochloric acid
6. 6
   Extraktionextracted with methyl tert-butyl ether three times
7. 7
   Waschenwashed with an aqueous saturated sodium chloride solution
8. 8
   Trocknendried over magnesium sulfate
9. 9
   Einengenconcentrated under reduced pressure

Vorschrift

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:

Quelle