Trifluoroacetic acid → HCID 23114669, compound

HRID 2080388Notes

Reaction equation

HRID 2080388 reaction equation
FC(F)(F)C(O)=O.C(OC(O[CH:16]([C:30]1[CH:35]=[C:34]([F:36])[CH:33]=[CH:32][C:31]=1[F:37])[C:17]1[N:18]([C:22]2[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=2)[CH:19]=[CH:20][N:21]=1)=O)(C)(C)C.[Cl:38][C:39]1[CH:44]=[CH:43][C:42]([SH:45])=[CH:41][CH:40]=1.C(=O)([O-])[O-].[K+].[K+]>C(OCC)C>[Cl:38][C:39]1[CH:44]=[CH:43][C:42]([S:45][CH:16]([C:30]2[CH:35]=[C:34]([F:36])[CH:33]=[CH:32][C:31]=2[F:37])[C:17]2[N:18]([C:22]3[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=3)[CH:19]=[CH:20][N:21]=2)=[CH:41][CH:40]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 7815p-ChlorothiophenolHCID 11430Potassium CarbonateHCID 23114819HCID 23114819, compound

Product 1

HCID 23114669HCID 23114669, compoundYield 75.5%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

Trifluoroacetic acid (10 ml) was added to the 2-[(t-butoxycarbonyloxy)-(2,5-difluorophenyl)methyl]-1-(4-methoxyphenyl)-1H-imidazole (667 mg, 1.6 mmol) obtained in Referential Example 16. The resulting mixture was stirred at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure. Dioxane was added to the residue, followed by further concentration under reduced pressure. The residue was dissolved in thionyl chloride (2.0 ml) and to the resulting solution was added a drop of dimethylformamide. The resulting mixture was stirred at room temperature for 17 hours. The reaction mixture was concentrated under reduced pressure. To the residue was added dioxane, followed by further concentration under reduced pressure. The residue was dissolved in dimethylformamide (5.0 ml). To the resulting solution were added 4-chlorobenzenethiol (347 mg, 2.4 mmol) and potassium carbonate (1.32 g, 9.6 mmol). The resulting mixture was stirred at 50° C. for 2 hours. After the reaction mixture was allowed to stand until it became room temperature, ethyl ether (60 ml) was added thereto. The resulting mixture was washed with water and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (hexane:ethyl acetate=10:1 to 5:1), followed by crystallization from ethanol to give the title compound (535 mg, 75%) as colorless needle crystals.

Workup

  1. customobtained in Referential Example 16
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. additionDioxane was added to the residue
  4. concentrationfollowed by further concentration under reduced pressure
  5. dissolutionThe residue was dissolved in thionyl chloride (2.0 ml) and to the resulting solution
  6. additionwas added a drop of dimethylformamide
  7. stirringThe resulting mixture was stirred at room temperature for 17 hours
  8. concentrationThe reaction mixture was concentrated under reduced pressure
  9. additionTo the residue was added dioxane
  10. concentrationfollowed by further concentration under reduced pressure
  11. dissolutionThe residue was dissolved in dimethylformamide (5.0 ml)
  12. stirringThe resulting mixture was stirred at 50° C. for 2 hours
  13. custombecame room temperature
  14. washThe resulting mixture was washed with water and brine
  15. dry with materialdried over anhydrous magnesium sulfate
  16. concentrationconcentrated under reduced pressure
  17. customThe residue was purified by silica gel chromatography (hexane:ethyl acetate=10:1 to 5:1)
  18. customfollowed by crystallization from ethanol

Sources & evidence

ORD record
ord-ee066be6b2164431b97bc52a8d648e99
Source dataset
uspto-grants-2011_04
Patent number
US07932271B2

Reaction notes

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