Iodine → 2-(5-Iodo-1H-pyrazol-1-yl)ethan-1-ol

Temperatur

0 °C

To a cold (0° C.) solution of 2-pyrazol-1-yl-ethanol (0.5 g, 4.46 mmol) in tetrahydrofuran (15 mL), under an atmosphere of nitrogen, was added N,N,N′,N′-tetramethyl-ethylenenediamine (1.34 ml, 8.92 mmol, 2.0 eq.) followed by n-butyllithium (2.5M in hexane, 4.0 ml, 10 mmol, 2.2 eq.) at such a rate as to maintain the temperature below 5° C. The resulting yellow solution was stirred at 0° C. for 0.5 hr before adding a solution of iodine (1.36 g, 5.35 mmol, 1.2 eq.) in tetrahydrofuran (10 mL). The resulting mixture was stirred for 20 min before concentrating the mixture by evaporation under reduced pressure. The residue was partition between ethyl acetate (50 mL) and aqueous citric acid (1M, 100 ml). The organic phase was washed with 10% aqueous sodium thiosulphate solution, saturated brine (20 mL) and dried over sodium sulphate. The resulting mixture was filtered and the filtrate concentrated under reduced pressure to give a brown oil. The crude oil was purified by chromatography on silica gel (60 g) eluting with a gradient of ethyl acetate in heptane (50:50) to give the title compound as a white solid (0.4 g, 38%).

1. temperatureto maintain the temperature below 5° C
2. stirringThe resulting mixture was stirred for 20 min
3. concentrationbefore concentrating the mixture
4. customby evaporation under reduced pressure
5. customThe residue was partition between ethyl acetate (50 mL) and aqueous citric acid (1M, 100 ml)
6. washThe organic phase was washed with 10% aqueous sodium thiosulphate solution, saturated brine (20 mL)
7. dry with materialdried over sodium sulphate
8. filtrationThe resulting mixture was filtered
9. concentrationthe filtrate concentrated under reduced pressure
10. customto give a brown oil
11. customThe crude oil was purified by chromatography on silica gel (60 g)
12. washeluting with a gradient of ethyl acetate in heptane (50:50)

ORD-Eintrag

ord-ba3ca4302ab34d52987e1c5edb8d07b5

Quelldatensatz

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08916593B2