Chlorodifluoromethane → Tert-butyl 4-(2-(difluoromethoxy)-5-iodobenzoyl)piperazine-1-carboxylate

A stirred slurry of tert-butyl 4-(2-hydroxy-5-iodobenzoyl)piperazine-1-carboxylate (7.06 g, 16.33 mmol) and potassium hydroxide (30% aqueous, 120 mL) in 2-propanol (200 mL) at 50° C. was treated with chlorodifluoromethane by bubbling a stream of the gaseous reagent through the stirring reaction mixture for 6 min. The reaction mixture was placed in a Parr high pressure reaction vessel, heated at 80° C. for 16 h and then cooled to ambient temperature. The resulting solution was concentrated to remove 2-propanol and the aqueous portion was extracted with ethyl acetate (3×200 mL). The organic portions were dried (Na2SO4) and concentrated. The residue was purified by reverse phase HPLC to give 5.55 g of tert-butyl 4-(2-(difluoromethoxy)-5-iodobenzoyl)piperazine-1-carboxylate as a white solid.

1. customby bubbling a stream of the gaseous reagent
2. customthrough the stirring reaction mixture for 6 min
3. customThe reaction mixture was placed in a Parr high pressure reaction vessel
4. temperaturecooled to ambient temperature
5. concentrationThe resulting solution was concentrated
6. customto remove 2-propanol
7. extractionthe aqueous portion was extracted with ethyl acetate (3×200 mL)
8. dry with materialThe organic portions were dried (Na2SO4)
9. concentrationconcentrated
10. customThe residue was purified by reverse phase HPLC

ORD-Eintrag

ord-02cb7ad356d8422aae186bde3fb3bbe1

Quelldatensatz

uspto-grants-2010_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07825120B2