Thiophenol → HCID 86670451, compound

HRID 1972700Notes

Reaction equation

HRID 1972700 reaction equation
CS(O[CH2:6][C@@H:7]1[N:12]([C:13]2[CH:18]=[CH:17][C:16]([C:19]([OH:28])([C:24]([F:27])([F:26])[F:25])[C:20]([F:23])([F:22])[F:21])=[CH:15][CH:14]=2)[CH2:11][CH2:10][N:9]([C:29]([O-:31])=[O:30])[CH2:8]1)(=O)=O.C(=O)([O-])[O-].[K+].[K+].[C:38]1([SH:44])[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1>C(#N)C>[C:38]1([S:44][CH2:6][C@@H:7]2[N:12]([C:13]3[CH:18]=[CH:17][C:16]([C:19]([OH:28])([C:24]([F:25])([F:26])[F:27])[C:20]([F:23])([F:21])[F:22])=[CH:15][CH:14]=3)[CH2:11][CH2:10][N:9]([C:29]([O:31][C:16]([CH3:19])([CH3:17])[CH3:15])=[O:30])[CH2:8]2)[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1

Participants

5

Reactant 3

HCID 7969ThiophenolHCID 11430Potassium CarbonateHCID 86670452HCID 86670452, compound

Product 1

HCID 86670451HCID 86670451, compoundYield 122.8%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
120 °C

Procedure

A 5 mL vial was charged with (3R)-3-(((methylsulfonyl)oxy)methyl)-4-(4-(2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl)phenyl)-1-piperazinecarboxylate (0.300 g, 0.559 mmol), potassium carbonate (0.190 g, 1.38 mmol), benzenethiol (0.070 mL, 0.69 mmol, Sigma-Aldrich, St. Louis, Mo.) and acetonitrile (2 mL). The reaction mixture was heated in an Initiator microwave reactor (Biotage AB, Inc., Uppsala, Sweden) at 120° C. for 30 min. The reaction mixture was partitioned between water (20 mL) and EtOAc (20 mL). The aqueous phase was extracted with EtOAc (20 mL). The combined organic phases were washed with saturated aqueous NaCl (40 mL). The organic phase was dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by column chromatography (25 g of silica, 0-30% EtOAc in hexanes) to afford tert-butyl (3R)-3-((phenylsulfanyl)methyl)-4-(4-(2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl)phenyl)-1-piperazinecarboxylate (0.189 g) as a white solid.

Workup

  1. customThe reaction mixture was partitioned between water (20 mL) and EtOAc (20 mL)
  2. extractionThe aqueous phase was extracted with EtOAc (20 mL)
  3. washThe combined organic phases were washed with saturated aqueous NaCl (40 mL)
  4. dry with materialThe organic phase was dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by column chromatography (25 g of silica, 0-30% EtOAc in hexanes)

Sources & evidence

ORD record
ord-dcd49e3378904b5e938a6890de8bb910
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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