反应详情

X-Zyme 6134 (20%, 90 mg) was added to a suspension of 2-methyl-2H-pyrazole-3,4-dicarboxylic acid diethyl ester (as prepared in Example 10, Step 1, 4.5 g, 19.5 mmol) in KPI (100 mM, pH 7.2, 450 ml). Sodium hydroxide solution (1 M, total amount 23.2 ml) was added slowly as needed to keep the pH constantly at 7.2 over the course of the reaction. After 18.5 h, the reaction mixture was extracted with tert-butyl methyl ether (TBME) to remove unwanted byproducts. The water layer was then acidified (pH 3.9) by addition of H2SO4, and extracted several times with TBME. During these extractions, the pH of the water layer was adjusted by addition of H2SO4 to a pH range between 4.2 and 3.8. After drying (Na2SO4) and evaporating the combined organic layers, a first crop of title compound (2.90 g, 74%) was obtained as a light grey solid. An additional crop of title compound (0.21 g, 5.3%) was obtained by adding brine to the water layer, repeated extraction with TBME, drying (Na2SO4) of the combined organic layers, and evaporation.

1. customover the course of the reaction
2. extractionthe reaction mixture was extracted with tert-butyl methyl ether (TBME)
3. customto remove unwanted byproducts
4. additionby addition of H2SO4
5. extractionextracted several times with TBME
6. extractionDuring these extractions
7. additionthe pH of the water layer was adjusted by addition of H2SO4 to a pH range between 4.2 and 3.8
8. dry with materialAfter drying (Na2SO4)
9. customevaporating the combined organic layers