(6R-trans)-1-chloro-N-[2-chloro-4-fluoro-5-(tetrahydro-6-hydroxy-1,3-dioxo-1H-pyrrolo[1,2-c]imidazol-2(3H)-yl)phenyl]methanesulfonamide → Profluazol

HRID 432959Notes

Reaction equation

HRID 432959 reaction equation
[Cl:1][CH2:2][S:3]([NH:6][C:7]1[CH:12]=[C:11]([N:13]2[C:17](=[O:18])[C@H:16]3[CH2:19][C@@H:20](O)[CH2:21][N:15]3[C:14]2=[O:23])[C:10]([F:24])=[CH:9][C:8]=1[Cl:25])(=[O:5])=[O:4].[F:26]C(N(CC)CC)(F)C(F)F>ClCCCl>[Cl:1][CH2:2][S:3]([NH:6][C:7]1[CH:12]=[C:11]([N:13]2[C:17](=[O:18])[C@H:16]3[CH2:19][C@H:20]([F:26])[CH2:21][N:15]3[C:14]2=[O:23])[C:10]([F:24])=[CH:9][C:8]=1[Cl:25])(=[O:5])=[O:4]

Participants

4

Reactant 2

HCID 10982513(6R-trans)-1-chloro-N-[2-chloro-4-fluoro-5-(tetrahydro-6-hydroxy-1,3-dioxo-1H-pyrrolo[1,2-c]imidazol-2(3H)-yl)phenyl]methanesulfonamideHCID 122432061,1,2,2-Tetrafluoroethyldiethylamine

Product 1

HCID 11037075Profluazol

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
50 °C

Procedure

In a Teflon® flask, a suspension of (6R-trans)-1-chloro-N-[2-chloro4-fluoro-5-(tetrahydro-6-hydroxy-1,3-dioxo-1H-pyrrolo[1,2-c]imidazol-2(3H)-yl)phenyl]methanesulfonamide (8.24 g, assay 94.5% pure, 18.9 mmol) in 1,2-dichloroethane (40 mL) was heated to reflux and then 1,1,2,2-tetrafluoroethyldiethylamine (3.8 g, 26 mmol) was added over 1-2 minutes. Refluxing was continued for 1 hour, then 20 mL of the solvent was distilled out of the reaction mixture at atmospheric pressure. The reaction mixture was cooled to 50° C., 1-propanol (1 mL) was added, the pressure was reduced to about 20 kPa (150 mm Hg) for 10 minutes, and then the remaining solvent was distilled off at 55-60° C. at 20 kPa (150 mm Hg). More l-propanol (15 mL) was added at 60° C., then the mixture was cooled slowly to room temperature, and stirred overnight at room temperature to complete the crystallization. The mixture was filtered and the solids were rinsed with several portions of 1-propanol (10 mL total) and dried to afford 6.57 g (79.3% crude yield) of the title compound as a white powder melting at 166-168° C. (purity: 97.3% by HPLC).

Workup

  1. temperaturewas heated
  2. temperatureto reflux
  3. temperatureRefluxing
  4. distillation20 mL of the solvent was distilled out of the reaction mixture at atmospheric pressure
  5. addition1-propanol (1 mL) was added
  6. waitthe pressure was reduced to about 20 kPa (150 mm Hg) for 10 minutes
  7. distillationthe remaining solvent was distilled off at 55-60° C. at 20 kPa (150 mm Hg)
  8. additionMore l-propanol (15 mL) was added at 60° C.
  9. temperaturethe mixture was cooled slowly to room temperature
  10. customthe crystallization
  11. filtrationThe mixture was filtered
  12. washthe solids were rinsed with several portions of 1-propanol (10 mL total)
  13. customdried

Sources & evidence

ORD record
ord-c411a7244e8b4cc59ea837d65f71369f
Source dataset
uspto-grants-2003_12
Patent number
US06664400B2

Reaction notes

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