Hydrochloric Acid → 3-Phenyl-1-(toluene-4-sulfonyl)-1H-indole-2-carboxylic acid ethyl ester

HRID 242872Notes

Reaction equation

HRID 242872 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[NH:7][C:8]2[C:13]([C:14]=1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[CH:12][CH:11]=[CH:10][CH:9]=2)=[O:5])[CH3:2].[H-].[Na+].[CH3:23][C:24]1[CH:29]=[CH:28][C:27]([S:30](Cl)(=[O:32])=[O:31])=[CH:26][CH:25]=1.Cl>CN(C=O)C>[CH2:1]([O:3][C:4]([C:6]1[N:7]([S:30]([C:27]2[CH:28]=[CH:29][C:24]([CH3:23])=[CH:25][CH:26]=2)(=[O:32])=[O:31])[C:8]2[C:13]([C:14]=1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[CH:12][CH:11]=[CH:10][CH:9]=2)=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 73974-Toluenesulfonyl chlorideHCID 24758Sodium hydrideHCID 2763656ethyl 3-phenyl-1H-indole-2-carboxylate

Product 1

HCID 681575273-Phenyl-1-(toluene-4-sulfonyl)-1H-indole-2-carboxylic acid ethyl esterYield 52%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a stirred solution of 3-phenyl-1H-indole-2-carboxylic acid ethyl ester (3.99 g, 15.0 mmol) in DMF (25 mL) cooled to 0° C. and under a nitrogen atmosphere was added NaH (60% in mineral oil, 720 mg, 18.0 mmol). After stirring for 10 min at RT, the reaction mixture was cooled to 0° C. and 4-methylbenzenesulfonyl chloride (3.44 g, 18.0 mmol) in DMF (15 mL) added. Stirring was continued for 16 h at RT then the mixture was poured into 1.0M HCl and extracted with EtOAc (×2). The combined organic fractions were washed with water, dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 30-100% DCM in pentane) affording the title compound as a colourless oil (3.25 g, 52%). 1H NMR (CDCl3, 400 MHz): δ 8.08 (1H, d, J=8.43 Hz), 7.92 (2H, d, J=8.37 Hz), 7.53-7.36 (7H, m), 7.28-7.21 (3H, m), 4.35 (2H, q, J=7.15 Hz), 2.36 (3H, s), 1.25 (3H, t, J=7.14 Hz)

Workup

  1. temperaturethe reaction mixture was cooled to 0° C.
  2. stirringStirring
  3. waitwas continued for 16 h at RT
  4. extractionextracted with EtOAc (×2)
  5. washThe combined organic fractions were washed with water
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated in vacuo
  8. customThe resulting residue was purified by column chromatography (Si—PCC, gradient 30-100% DCM in pentane)

Sources & evidence

ORD record
ord-9ec196f9223e4095994b151c32e515dd
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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