Tetrahydrofuran → 3-iodo-1-(oxetan-3-yl)-1H-pyrazole

3-iodo-1H-pyrazole (503 mg, 2.6 mmol) was added as a solution in DMF (1 mL) to a 1.0 M THF solution of NaHMDS (2.9 mL, 2.9 mmol) that had been pre-cooled in an ice water bath. Additional portions of DMF (2×1 mL) were used to ensure complete transfer. 3-iodooxetane (0.41 mL, 4.7 mmol) was added in one portion and the reaction mixture was allowed to warm to r.t. After 1 h, the reaction mixture was heated to 45° C. and allowed to stir for an additional 75 h. The mixture was cooled and diluted with EtOAc, and water. The aqueous phase was extracted with EtOAc. The combined organic phase was washed with water and were dried over Na2SO4, filtered and concentrated to afford a crude residue that was purified by silica gel chromatography (0-30% EtOAc in hexanes) to provide 3-iodo-1-(oxetan-3-yl)-1H-pyrazole 7.53 (414 mg). Regiochemistry was confirmed as drawn via NOE studies. LCMS-ESI+ (m/z): [M+H]+ calcd for C6H8IN2O: 251.0; found: 251.0.

1. temperaturehad been pre-cooled in an ice water bath
2. temperaturethe reaction mixture was heated to 45° C.
3. temperatureThe mixture was cooled
4. extractionThe aqueous phase was extracted with EtOAc
5. washThe combined organic phase was washed with water
6. dry with materialwere dried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated
9. customto afford a crude residue that
10. customwas purified by silica gel chromatography (0-30% EtOAc in hexanes)

ORD-Eintrag

ord-e46bae3e89214ba4bfb9cc6b9c04c376

Quelldatensatz

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09376441B2