Reaction #1256779

Reaction equation

tert-butyl 4-(2-hydroxy-5-iodobenzoyl)piperazine-1-carboxylate

potassium hydroxide

chlorodifluoromethane

→

tert-butyl 4-(2-(difluoromethoxy)-5-iodobenzoyl)piperazine-1-carboxylate

Solvents

2-propanol

Conditions

Workup

1. 1
   Otherby bubbling a stream of the gaseous reagent
2. 2
   Otherthrough the stirring reaction mixture for 6 min
3. 3
   OtherThe reaction mixture was placed in a Parr high pressure reaction vessel
4. 4
   Temperaturecooled to ambient temperature
5. 5
   ConcentrationThe resulting solution was concentrated
6. 6
   Otherto remove 2-propanol
7. 7
   Extractionthe aqueous portion was extracted with ethyl acetate (3×200 mL)
8. 8
   DryingThe organic portions were dried (Na2SO4)
9. 9
   Concentrationconcentrated
10. 10
    OtherThe residue was purified by reverse phase HPLC

Procedure

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.

Source