Hydrochloric Acid → 3-(4-chlorophenoxy)-2-methyl-5-(methylthio)-1H-indole

HRID 2233747

Reaction equation

HRID 2233747 reaction equation
[Cl:1][C:2]1[CH:12]=[CH:11][C:5]([O:6][CH2:7][C:8](=O)[CH3:9])=[CH:4][CH:3]=1.Cl.[CH3:14][S:15][C:16]1[CH:21]=[CH:20][C:19]([NH:22]N)=[CH:18][CH:17]=1.Cl>CC#N>[Cl:1][C:2]1[CH:12]=[CH:11][C:5]([O:6][C:7]2[C:20]3[C:19](=[CH:18][CH:17]=[C:16]([S:15][CH3:14])[CH:21]=3)[NH:22][C:8]=2[CH3:9])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 2398741-(4-Chlorophenoxy)acetoneHCID 2760977(4-(Methylsulfanyl)phenyl)hydrazine hydrochloride

Product 1

HCID 686171473-(4-chlorophenoxy)-2-methyl-5-(methylthio)-1H-indole

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
50 °C

Procedure

1-(4-Chloro-phenoxy)-propan-2-one (2.66 g) was added to a stirred solution of [4-(methylthio)phenyl]-hydrazine hydrochloride (2.5 g) in MeCN (15 ml)/HCl (0.5M, 15 ml) at RT. The reaction was stirred at 50° C. for 1 h. After cooling to room temperature, the reaction was partitioned between ethylacetate/water, the organics were separated, washed with aq sodium hydroxide (1 M), dried and evaporated under reduced pressure. The residue was purified by chromatography on silica eluting with 5-20% ethylacetate/iso-hexane. The resulting hydrazone was dissolved in THF (80 ml). Sodium bicarbionate solid (1.04 g) was added followed by phosphorus trichloride (0.41 ml) dropwise, and the reaction stirred at RT for 2 h. Further phosphorus trichloride (1.20 ml) was added dropwise, and the reaction stirred at RT for 16 h. The reaction was quenched with water. The mixture was extracted with ethylacetate, the organics washed with aq. sodium hydrogencarbonate, brine, dried and evaporated under reduced pressure. The residue was purified by chromatography on silica eluting with 5-10% ethylacetate/iso-hexane. Yield 0.45 g.

Workup

  1. temperatureAfter cooling to room temperature
  2. customthe reaction was partitioned between ethylacetate/water
  3. customthe organics were separated
  4. washwashed with aq sodium hydroxide (1 M)
  5. customdried
  6. customevaporated under reduced pressure
  7. customThe residue was purified by chromatography on silica eluting with 5-20% ethylacetate/iso-hexane
  8. dissolutionThe resulting hydrazone was dissolved in THF (80 ml)
  9. additionSodium bicarbionate solid (1.04 g) was added
  10. stirringthe reaction stirred at RT for 2 h
  11. additionFurther phosphorus trichloride (1.20 ml) was added dropwise
  12. stirringthe reaction stirred at RT for 16 h
  13. customThe reaction was quenched with water
  14. extractionThe mixture was extracted with ethylacetate
  15. washthe organics washed with aq. sodium hydrogencarbonate, brine
  16. customdried
  17. customevaporated under reduced pressure
  18. customThe residue was purified by chromatography on silica eluting with 5-10% ethylacetate/iso-hexane

Sources & evidence

ORD record
ord-b92b96d35dcd4878af312445a5f834de
Source dataset
uspto-grants-2010_05
Patent number
US07709521B2

Linked notes

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