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

HRID 1169597Notes

Reaction equation

HRID 1169597 reaction equation
[OH:1][C:2]1[CH:22]=[CH:21][C:20]([I:23])=[CH:19][C:3]=1[C:4]([N:6]1[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][CH2:7]1)=[O:5].[OH-].[K+].Cl[CH:27]([F:29])[F:28]>CC(O)C>[F:28][CH:27]([F:29])[O:1][C:2]1[CH:22]=[CH:21][C:20]([I:23])=[CH:19][C:3]=1[C:4]([N:6]1[CH2:7][CH2:8][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:10][CH2:11]1)=[O:5]

Participants

5

Reactant 3

HCID 6372ChlorodifluoromethaneHCID 14797Potassium HydroxideHCID 31121968Tert-butyl 4-(2-hydroxy-5-iodobenzoyl)piperazine-1-carboxylate

Product 1

HCID 68763115Tert-butyl 4-(2-(difluoromethoxy)-5-iodobenzoyl)piperazine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
80 °C

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.

Workup

  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

Sources & evidence

ORD record
ord-02cb7ad356d8422aae186bde3fb3bbe1
Source dataset
uspto-grants-2010_11
Patent number
US07825120B2

Reaction notes

Loading…