Water → Indole

HRID 1666736Notes

Reaction equation

HRID 1666736 reaction equation
C(OC([C:6]1[NH:7][C:8]2[C:13]([CH:14]=1)=[CH:12][C:11](Cl)=[CH:10][CH:9]=2)=O)C.[H-].[Na+].C1(S(Cl)(=O)=O)C=CC=CC=1.O>CN(C=O)C>[NH:7]1[C:8]2[C:13](=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:14]=[CH:6]1

Participants

6

Reactant 4

HCID 962WaterHCID 7369Benzenesulfonyl chlorideHCID 24758Sodium hydrideHCID 78518Ethyl 5-chloroindole-2-carboxylate

Product 1

HCID 798IndoleYield 90%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred and cooled (0° C.) solution of ethyl-5-chloroindole-2-carboxylate (1.052 g, 4.70 mmol) in DMF (25 mL) under N2, was added NaH (60% in oil, 230 mg, 5.64 mmol) portionwise. After the end of gas evolution, phenylsulfonyl chloride (0.72 mL, 5.64 mmol) was added. The reaction mixture was stirred for 1H (TLC monitoring, eluant dichloromethane). A little amount of water was added carefully and DMF was evaporated. Crude residue was dissolved in EtOAc and washed with water and brine. After drying and evaporation of solvents the compound was purified by chromatography on silica gel (eluant:cyclohexane/EtOAc 9/1 to 7/3) to afford protected indole (1.547 g, 90% yield. Off-white solid; 1H NMR (d6-DMSO) δ 1.30 (t, J=7.2 Hz, 3H), 4.35 (q, J=7.2 Hz, 2H), 7.37 (s, 1H), 7.53 (dd, J=2.2 and 9.1 Hz), 7.62-7.77 (m, 3H), 7.80 (d, J=2.2 Hz, 1H), 7.99 (m, 2H), 8.06 (d, J=9.1 Hz); MS (ESI, El+) m/z=364 (MH+).

Workup

  1. stirringThe reaction mixture was stirred for 1H (TLC monitoring, eluant dichloromethane)
  2. customDMF was evaporated
  3. dissolutionCrude residue was dissolved in EtOAc
  4. washwashed with water and brine
  5. customAfter drying
  6. customevaporation of solvents the compound
  7. customwas purified by chromatography on silica gel (eluant:cyclohexane/EtOAc 9/1 to 7/3)

Sources & evidence

ORD record
ord-70bb42c223c84c8f939f581679d97298
Source dataset
uspto-grants-2011_10
Patent number
US08044091B2

Reaction notes

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