反应详情

To a 20 L four-neck bottle, 4-bromo-(tert-butyl)pyrazole (1.15 kg, 5.66 mol) and THF (9.2 L) were added, then the mixture was cooled to between −78° C. and −85° C. and treated with nBuLi (6.23 mol) dropwise at that temperature. After addition the solution was stirred at the same temperature for 1 h and isopropyl pinacol borate (1.47 kg, 7.92 mol) was added dropwise. The reaction was complete after stirring for ˜3 h (starting material<1.0% a/a by GC) then water (2.3 L) was added to quench the reaction; and the pH adjusted to 8-9 by addition of 3.45 kg 1M HCl. The aqueous phase was extracted with TBME (3.45 L×2), and the combined organic phase washed with 5% NaCl (3.45 L×2) and water (3.45 L) in sequence. The organic phase was evaporated to give the crude product. After subsequent recrystallization from heptanes the pure product was obtained as a white solid (GC purity 99.7% a/a) in a 63.5% th overall yield. (Two 20 L reactions were run, then combined in the heptane recrystallization).

1. temperaturethe mixture was cooled to between −78° C. and −85° C.
2. additionAfter addition the solution
3. stirringafter stirring for ˜3 h (starting material<1.0% a/a by GC)
4. customto quench
5. customthe reaction
6. extractionThe aqueous phase was extracted with TBME (3.45 L×2)
7. washthe combined organic phase washed with 5% NaCl (3.45 L×2) and water (3.45 L) in sequence
8. customThe organic phase was evaporated