反应详情

温度

-78 °C

The 2-(1-methyl-1H-pyrazol-5-yl)ethanol used as starting material was prepared as follows:—n-Butyl lithium (1.6M in hexanes) (1226 mL, 1961.78 mmol) was added dropwise to 1-methyl-1H-pyrazole (153.4 g, 1868.37 mmol) in THF (3000 mL) cooled to −78° C. over a period of 1 hour under nitrogen. The resulting solution was stirred at −60° C. for 30 minutes, then warmed to −10° C. and stirred for a further 40 minutes. A solution of oxirane (210 mL, 4203.82 mmol) in THF (600 mL) was added slowly at −10° C. followed by further THF (1000 mL) and the resulting slurry was stirred at −10° C. for 30 minutes, then at 0° C. for 30 minutes. The mixture was then allowed to gradually warm to room temp under nitrogen and stirred for 16 hours. The reaction mixture was quenched with saturated NH4Cl solution (2000 ml), the layers separated and the aqueous phase extracted with n-butanol (3×1000 ml). The combined organics were washed with saturated brine (1500 ml), dried over MgSO4, filtered and evaporated to give an oil, which was azeotroped with toluene (1000 ml) to leave an oil with some solid. The oil was dissolved in DCM and the insoluble solid was filtered off and washed with DCM. The filtrate was purified by chromatography using a silica Novasep prep HPLC column, eluting with a gradient of 5-10% methanol in DCM. Pure fractions were evaporated to dryness to afford 2-(1-methyl-1H-pyrazol-5-yl)ethanol (195 g, 83%) as an oil.

1. customwas prepared
2. temperaturewarmed to −10° C.
3. stirringstirred for a further 40 minutes
4. stirringthe resulting slurry was stirred at −10° C. for 30 minutes
5. waitat 0° C. for 30 minutes
6. temperatureto gradually warm to room temp under nitrogen
7. stirringstirred for 16 hours
8. customThe reaction mixture was quenched with saturated NH4Cl solution (2000 ml)
9. customthe layers separated
10. extractionthe aqueous phase extracted with n-butanol (3×1000 ml)
11. washThe combined organics were washed with saturated brine (1500 ml)
12. dry with materialdried over MgSO4
13. filtrationfiltered
14. customevaporated
15. customto give an oil, which
16. customwas azeotroped with toluene (1000 ml)
17. customto leave an oil with some solid
18. filtrationthe insoluble solid was filtered off
19. washwashed with DCM
20. customThe filtrate was purified by chromatography
21. washeluting with a gradient of 5-10% methanol in DCM
22. customPure fractions were evaporated to dryness