4-Toluenesulfonyl chloride → HCID 19372765, compound

HRID 129221Notes

Reaction equation

HRID 129221 reaction equation
C([CH:3]([CH2:7][C:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([O:17][CH3:18])[CH:15]=2)[NH:10][CH:9]=1)[C:4]([OH:6])=[O:5])C.[H-].[Na+].[C:21]1([CH3:31])[CH:26]=[CH:25][C:24]([S:27](Cl)(=[O:29])=[O:28])=[CH:23][CH:22]=1>C1COCC1.CN(C=O)C>[CH3:18][O:17][C:14]1[CH:15]=[C:16]2[C:11](=[CH:12][CH:13]=1)[N:10]([S:27]([C:24]1[CH:25]=[CH:26][C:21]([CH3:31])=[CH:22][CH:23]=1)(=[O:29])=[O:28])[CH:9]=[C:8]2[CH2:7][CH2:3][C:4]([OH:6])=[O:5]

Participants

6

Reactant 3

HCID 73974-Toluenesulfonyl chlorideHCID 24758Sodium hydrideHCID 19372785HCID 19372785, compound

Product 1

HCID 19372765HCID 19372765, compoundYield 32,926.398%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8028TetrahydrofuranSolvent2×

Procedure

In THF(640 ml)-DMF(130 ml) was dissolved ethyl 3-(5-methoxy-1H-indol-3-yl)propionic acid (99.3 g, 0.4 mol). To the solution was added in limited amounts, under ice-cooling, a suspension of 60% sodium hydride in oil (18.4 g, 0.46 mol) in THF(50 ml)-DMF(10 ml). The mixture was stirred at room temperature for one hour, and the mixture was again cooled with ice. To the mixture was gradually added p-toluenesulfonyl chloride (83.9 g, 0.44 mmol), followed by stirring for a further 3 hours at room temperature. The reaction mixture was poured into an ice-saturated NH4Cl solution (180 ml). The upper layer was subjected to extraction with ethyl acetate (100 ml+500 ml). The extract solution was washed with a saturated aqueous saline solution (300 ml×2), followed by drying over Na2SO4. The residue was purified by means of silica gel chromatography (eluent: hexane-ethyl acetate (2:1)) and then were added hydrochloric acid (100 ml) and acetic acid (400 ml), and was refluxed for 1 hour. The reaction mixture was concentrated and the resulting crystals were washed with water, dried under reduced pressure and washed with methanol-isopropyl ether (1:3) to obtain the title compound (54.1 g: m.p. 172°-174° C.)

Workup

  1. additionTo the solution was added in limited amounts, under ice-
  2. temperaturecooling
  3. temperaturethe mixture was again cooled with ice
  4. stirringby stirring for a further 3 hours at room temperature
  5. extractionThe upper layer was subjected to extraction with ethyl acetate (100 ml+500 ml)
  6. washThe extract solution was washed with a saturated aqueous saline solution (300 ml×2)
  7. dry with materialby drying over Na2SO4
  8. customThe residue was purified by means of silica gel chromatography (eluent: hexane-ethyl acetate (2:1))
  9. additionwere added hydrochloric acid (100 ml) and acetic acid (400 ml)
  10. temperaturewas refluxed for 1 hour
  11. concentrationThe reaction mixture was concentrated
  12. washthe resulting crystals were washed with water
  13. customdried under reduced pressure
  14. washwashed with methanol-isopropyl ether (1:3)

Sources & evidence

ORD record
ord-d406a1f3564b46599185bab6560ee84c
Source dataset
uspto-grants-1995_11
Patent number
US05466689

Reaction notes

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