Benzenesulfonyl chloride → (R)-3-(1-methyl-2-pyrrolidinylmethyl)-1-phenylsulfonylindole

HRID 1870966Notes

Reaction equation

HRID 1870966 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[CH3:11][N:12]1[CH2:16][CH2:15][CH2:14][C@@H:13]1[CH2:17][C:18]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[NH:20][CH:19]=1.[C:27]1([S:33](Cl)(=[O:35])=[O:34])[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>C1COCC1>[CH3:11][N:12]1[CH2:16][CH2:15][CH2:14][C@@H:13]1[CH2:17][C:18]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[N:20]([S:33]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)(=[O:35])=[O:34])[CH:19]=1

Participants

5

Reactant 3

HCID 7369Benzenesulfonyl chlorideHCID 2724254Sodium bis(trimethylsilyl)amideHCID 44397420(R)-3-((1-methylpyrrolidin-2-yl)methyl)-1H-indole

Product 1

HCID 11624561(R)-3-(1-methyl-2-pyrrolidinylmethyl)-1-phenylsulfonylindoleYield 46.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Sodium bis(trimethylsilyl)amide (0.25 mL, 1M in THF, 0.25 mmol) was added to a solution of (R)-3-(1-methyl-2-pyrrolidinylmethyl)-1H-indole (Example 3e, 25.8 mg, 0.12 mmol) in THF (1.5 mL) at -78° C. and the mixture was stirred for 1 h. Phenylsulfonyl chloride (50 μL, 0.39 mmol) was added and the mixture stirred at room temperature for 1 h. prior to quenching with water (6 drops) and silica gel (~1 g). Purification using solid phase extraction tubes (1000 mg silica) eluting with 2M methanolic ammonia in dichloromethane (0-4%) yielded (R)-3-(1-methyl-2-pyrrolidinylmethyl)-1-phenylsulfonylindole (19.7 mg, 46%, HRMS-FAB+ for C20H22N2O2S: calculated MH+ :355.14801; found MH+ :355.14837).

Workup

  1. stirringthe mixture stirred at room temperature for 1 h.
  2. customto quenching with water (6 drops) and silica gel (~1 g)
  3. customPurification
  4. extractionsolid phase extraction tubes (1000 mg silica)
  5. washeluting with 2M methanolic ammonia in dichloromethane (0-4%)

Sources & evidence

ORD record
ord-69dcccc4e40a4525850274015f534ac2
Source dataset
uspto-grants-2000_08
Patent number
US06100291

Reaction notes

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