Water → HCID 57952154, compound

HRID 603356Notes

Reaction equation

HRID 603356 reaction equation
[Cl:1][C:2]1[CH:8]=[CH:7][CH:6]=[C:5]([CH3:9])[C:3]=1[NH2:4].C1(C)C=CC(S(O)(=O)=O)=CC=1.C([O:23][C:24](=O)[CH:25]=[C:26]1[CH2:31][CH:30]([CH2:32][CH3:33])[CH2:29][CH2:28][C:27]1=O)C.O>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:8]=[CH:7][CH:6]=[C:5]([CH3:9])[C:3]=1[N:4]1[C:27]2[C:26]([CH2:31][CH:30]([CH2:32][CH3:33])[CH2:29][CH:28]=2)=[CH:25][C:24]1=[O:23]

Participants

6

Reactant 4

HCID 962WaterHCID 6101p-Toluenesulfonic acidHCID 68972-Chloro-6-methylanilineHCID 66883353HCID 66883353, compound

Product 1

HCID 57952154HCID 57952154, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
22 °C

Procedure

3.45 g of 2-Chloro-6-methyl-aniline are dissolved in 26 ml of toluene. 0.227 g of p-toluene-sulfonic acid (mono hydrate) are added and the mixture is heated to reflux. A solution of 5.0 g of (5-Ethyl-2-oxo-cyclohexylidene)-acetic acid ethyl ester in 13 ml of toluene is added drop-wise during 75 minutes and the water formed is collected by the means of a water separator. The reaction mixture is heated to reflux for 15 hours, during which time the condensing solvent is frequently removed and replaced by fresh toluene. For work-up, the mixture is cooled to 22° C. and is treated with 70 ml of saturated aqueous sodium bicarbonate solution under rigorous stirring. The layers are separated and the toluene phase is washed with a 5% aqueous solution of citric acid and finally with a 10% solution of sodium chloride in water. The aqueous phases are extracted with 70 ml of toluene and the toluene phases are combined. The solvent is evaporated in vacuo to yield 7.1 g of the crude product as a highly viscous oil. An analytical sample of the crude product can be purified by chromatography on silica gel using toluene/ethyl acetate (9:1) as eluent to yield pure 1-(2-Chloro-6-methyl-phenyl)-5-ethyl-1,4,5,6-tetrahydro-indol-2-one.

Workup

  1. temperaturethe mixture is heated to reflux
  2. customis collected by the means of a water separator
  3. temperatureThe reaction mixture is heated
  4. temperatureto reflux for 15 hours, during which time the condensing solvent
  5. customis frequently removed
  6. additionis treated with 70 ml of saturated aqueous sodium bicarbonate solution under rigorous stirring
  7. customThe layers are separated
  8. washthe toluene phase is washed with a 5% aqueous solution of citric acid and finally with a 10% solution of sodium chloride in water
  9. extractionThe aqueous phases are extracted with 70 ml of toluene
  10. customThe solvent is evaporated in vacuo
  11. customto yield 7.1 g of the crude product as a highly viscous oil
  12. customAn analytical sample of the crude product can be purified by chromatography on silica gel

Sources & evidence

ORD record
ord-618c0e20e0bb44b18a2c7008ab251a51
Source dataset
uspto-grants-2011_03
Patent number
US07906677B2

Reaction notes

Loading…