Ethylene Oxide → 2-(1-methyl-1H-pyrazol-5-yl)ethan-1-ol

Temperature

-78 °C

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

ORD record

ord-772dac578d054f27b802bd0b33c4511f

Source dataset

uspto-grants-2012_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08258140B2