Thiophenol → 1,1,1-trifluoro-2-(4-((2R)-2-((phenylsulfanyl)methyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-2-propanol

HRID 1972566Notes

Reaction equation

HRID 1972566 reaction equation
CS(O[CH2:6][C@H:7]1[CH2:12][N:11]([S:13]([C:16]2[S:17][CH:18]=[CH:19][CH:20]=2)(=[O:15])=[O:14])[CH2:10][CH2:9][N:8]1[C:21]1[CH:26]=[CH:25][C:24]([C:27]([OH:33])([CH3:32])[C:28]([F:31])([F:30])[F:29])=[CH:23][CH:22]=1)(=O)=O.C(=O)([O-])[O-].[K+].[K+].[C:40]1([SH:46])[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1>C(#N)C>[F:30][C:28]([F:31])([F:29])[C:27]([C:24]1[CH:23]=[CH:22][C:21]([N:8]2[CH2:9][CH2:10][N:11]([S:13]([C:16]3[S:17][CH:18]=[CH:19][CH:20]=3)(=[O:14])=[O:15])[CH2:12][C@@H:7]2[CH2:6][S:46][C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)=[CH:26][CH:25]=1)([OH:33])[CH3:32]

Participants

5

Reactant 3

HCID 7969ThiophenolHCID 11430Potassium CarbonateHCID 86670301((2R)-4-(2-thiophenylsulfonyl)-1-(4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-2-piperazinyl)methyl methanesulfonate2×

Product 1

HCID 569327221,1,1-trifluoro-2-(4-((2R)-2-((phenylsulfanyl)methyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-2-propanolYield 78%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
140 °C

Procedure

To a 5-mL microwave vial was added ((2R)-4-(thiophen-2-ylsulfonyl)-1-(4-(1,1,1-trifluoro-2-hydroxypropan-2-yl)phenyl)piperazin-2-yl)methyl methanesulfonate (0.200 g, 0.378 mmol, Intermediate B), potassium carbonate (0.105 g, 0.757 mmol), thiophenol (0.076 mL, 0.76 mmol, Aldrich, St. Louis, Mo.), and acetonitrile (3.0 mL). The vial was sealed and heated in an Initiator microwave reactor (Biotage AB, Inc., Uppsala, Sweden) at 140° C. for 40 min. The reaction mixture was filtered and the filtrate was concentrated. The crude product was purified by column chromatography (40 g of silica, 10 to 40% acetone in hexanes) to afford 1,1,1-trifluoro-2-(4-((2R)-2-((phenylsulfanyl)methyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-2-propanol (0.160 g) as a mixture of two isomers:

Workup

  1. customThe vial was sealed
  2. filtrationThe reaction mixture was filtered
  3. concentrationthe filtrate was concentrated
  4. customThe crude product was purified by column chromatography (40 g of silica, 10 to 40% acetone in hexanes)

Sources & evidence

ORD record
ord-08922177c3e343e5b8fee1435bb586f2
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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