4-Toluenesulfonyl chloride → 1-[(4-Methylphenyl)sulfonyl]-5-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine

HRID 887333Notes

Reaction equation

HRID 887333 reaction equation
[H-].[Na+].[S:3](Cl)([C:6]1[CH:12]=[CH:11][C:9]([CH3:10])=[CH:8][CH:7]=1)(=[O:5])=[O:4].[F:14][C:15]([F:26])([F:25])[C:16]1[CH:17]=[C:18]2[CH:24]=[CH:23][NH:22][C:19]2=[N:20][CH:21]=1>C1COCC1>[F:26][C:15]([F:14])([F:25])[C:16]1[CH:17]=[C:18]2[CH:24]=[CH:23][N:22]([S:3]([C:6]3[CH:12]=[CH:11][C:9]([CH3:10])=[CH:8][CH:7]=3)(=[O:5])=[O:4])[C:19]2=[N:20][CH:21]=1

Participants

5

Reactant 3

HCID 73974-Toluenesulfonyl chlorideHCID 24758Sodium hydrideHCID 307721175-Trifluoromethyl-1H-Pyrrolo[2,3-B]Pyridine

Product 1

HCID 497590301-[(4-Methylphenyl)sulfonyl]-5-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridineYield 92%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred solution of sodium hydride (6.2 g, 156 mmol, 60% dispersion), tosyl chloride (27 g, 141.8 mmol), in anhydrous THF (200 mL) under a nitrogen atmosphere was added a solution of 5-trifluoromethyl-lH-pyrrolo[2,3-b]pyridine (26.38 g, 141.8 mmol) in THF (150 mL) dropwise at a rate which maintained the internal temperature of the reaction below 40° C. The reaction mixture was stirred overnight at room temperature and analysis by LCMS showed no starting material remained after this time. The reaction mixture was concentrated to remove most of THF and diluted with DCM and water. The organic layer was separated and the aqueous layer further extracted with DCM. The organic layers are combined and washed with brine, dried over magnesium sulphate and concentrated to a volume which was appropriate to load onto the top of a silica plug (300 mL) pre-wet with DCM, and the silica was washed with 2.5 L DCM. The filtrate was concentrated to give the product as a slightly brown solid (44.1 g, 92% yield).

Workup

  1. temperaturemaintained
  2. customthe internal temperature of the reaction below 40° C
  3. concentrationThe reaction mixture was concentrated
  4. customto remove most of THF
  5. additiondiluted with DCM and water
  6. customThe organic layer was separated
  7. extractionthe aqueous layer further extracted with DCM
  8. washwashed with brine
  9. dry with materialdried over magnesium sulphate
  10. concentrationconcentrated to a volume which
  11. washthe silica was washed with 2.5 L DCM
  12. concentrationThe filtrate was concentrated

Sources & evidence

ORD record
ord-061bb4c6f7f34dbeb1d7fa322cdc4888
Source dataset
uspto-grants-2012_08
Patent number
US08247421B2

Reaction notes

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