Sodium hydride → 2-(5-chloro-6-(trifluoromethyl)-1H-indol-2-yl)-1-(4-fluorophenylthio)propan-2-ol

HRID 1616200Notes

Reaction equation

HRID 1616200 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([SH:8])=[CH:4][CH:3]=1.[H-].[Na+].[Cl:11][C:12]1[CH:13]=[C:14]2[C:18](=[CH:19][C:20]=1[C:21]([F:24])([F:23])[F:22])[N:17](S(C)(=O)=O)[C:16]([C:29]1([CH3:32])[CH2:31][O:30]1)=[CH:15]2>C1COCC1>[Cl:11][C:12]1[CH:13]=[C:14]2[C:18](=[CH:19][C:20]=1[C:21]([F:22])([F:24])[F:23])[NH:17][C:16]([C:29]([OH:30])([CH3:31])[CH2:32][S:8][C:5]1[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=1)=[CH:15]2

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 677894-FluorothiophenolHCID 589796055-chloro-1-methanesulfonyl-2-(2-methyl-oxiranyl)-6-trifluoromethyl-1H-indole

Product 1

HCID 444191882-(5-chloro-6-(trifluoromethyl)-1H-indol-2-yl)-1-(4-fluorophenylthio)propan-2-ol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

4-Fluoro-phenyl thiol (55 mg, 0.425 mmoL) was treated with NaH (60%, 17 mg, 0.425 mmoL) in THF (2 mL) at 0° C. After 10 min., 5-chloro-1-methanesulfonyl-2-(2-methyl-oxiranyl)-6-trifluoromethyl-1H-indole, the epoxide derivative compound prepared as in Example 72 (100 mg, 0.425 mmoL) in THF (1 mL) was added into the reaction via syringe. The reaction was slowly warmed to room temperature. THF was removed and the residue was partitioned between CH2Cl2 and water. The organic layer was washed with brine and dried over anhydrous Na2SO4, then concentrated to yield a crude white solid. The crude material was purified using column chromatography (silica gel, 3:1 hexanes:EtOAc as eluent) to yield the title compound as a white solid.

Workup

  1. additionwas added into the reaction via syringe
  2. customTHF was removed
  3. customthe residue was partitioned between CH2Cl2 and water
  4. washThe organic layer was washed with brine
  5. dry with materialdried over anhydrous Na2SO4
  6. concentrationconcentrated
  7. customto yield a crude white solid
  8. customThe crude material was purified

Sources & evidence

ORD record
ord-33d21a08f1e842ed97f3d49f250bb6bc
Source dataset
uspto-grants-2014_07
Patent number
US08765782B2

Reaction notes

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