Ethane → 2-Methyl-3-[gamma-(4-phenylpiperazino)propyl]indole

HRID 1580628Notes

Reaction equation

HRID 1580628 reaction equation
C([I:3])C.[Mg:4].[CH3:5][C:6]1[NH:7][C:8]2[C:13]([CH:14]=1)=[CH:12][CH:11]=[CH:10][CH:9]=2.[CH3:15][CH3:16].Cl[CH2:18][CH2:19][CH2:20][N:21]1[CH2:26][CH2:25][N:24]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH2:23][CH2:22]1.[Cl-].[NH4+]>C1(OC)C=CC=CC=1.C1C=CC=CC=1>[CH2:15]([Mg:4][I:3])[CH3:16].[CH3:5][C:6]1[NH:7][C:8]2[C:13]([C:14]=1[CH2:18][CH2:19][CH2:20][N:21]1[CH2:26][CH2:25][N:24]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[CH2:23][CH2:22]1)=[CH:12][CH:11]=[CH:10][CH:9]=2

Participants

10

Reactant 6

HCID 6324EthaneHCID 6340IodoethaneHCID 72242-MethylindoleHCID 25517Ammonium ChlorideHCID 139197Piperazine, 1-(3-chloropropyl)-4-phenyl-HCID 5462224Magnesium

Product 2

HCID 215633252-Methyl-3-[gamma-(4-phenylpiperazino)propyl]indoleHCID 178461634HCID 178461634, compound

Reagents, catalysts & solvents 2

HCID 241BenzeneSolventHCID 7519AnisoleSolvent2×

Conditions

Temperature
10 °C

Procedure

Ethylmagnesium iodide was prepared from 31.9 g of ethyl iodide and 5.0 g of magnesium in 100 ml of dry anisole and the mixture was heated for 1 hour at 50°-60°C. It was then cooled at 10°C, and while a solution of 2-methylindole (13.1 g) in dry anisole (50 ml) was added thereto, the temperature was maintained below 25°C. The mixture was then heated at 50°C until the evolution of ethane ceased. The resulting solution was cooled to -5°C in a cold bath, and a solution of 1-(γ-chloropropyl)-4-phenylpiperazine (52.5 g) in 100 ml of dry benzene was added during 1 hour at a temperature of -5° ± 2°C. The mixture was then stirred for 3 hours at -5°C and allowed to stand in a refrigerator overnight. The mixture was warmed to 20°-25°C for several hours. The precipitate was broken up and the mixture was poured into saturated aqueous ammonium chloride (500 ml) and stirred for 1 hour. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The organic solutions were combined and extracted three times with 10 % hydrochloric acid. The extracts were washed with ethyl acetate, cooled to 0°C, made alkaline with 50 % sodium hydroxide, and extracted three times with ethyl acetate. These extracts were dried over anhydrous sodium sulfate and evaporated to afford 2-methyl-3-[γ-(4-phenylpiperazino)propyl]indole as an oil which solidified by treating with benzene. Recrystallization from benzene gave needles, melting point 130.5°-131.5°C.

Workup

  1. temperaturethe mixture was heated for 1 hour at 50°-60°C
  2. temperaturethe temperature was maintained below 25°C
  3. temperatureThe resulting solution was cooled to -5°C in a cold bath
  4. customto stand in a refrigerator overnight
  5. temperatureThe mixture was warmed to 20°-25°C for several hours
  6. stirringstirred for 1 hour
  7. customThe organic layer was separated
  8. extractionthe aqueous layer was extracted with ethyl acetate
  9. extractionextracted three times with 10 % hydrochloric acid
  10. washThe extracts were washed with ethyl acetate
  11. temperaturecooled to 0°C
  12. extractionextracted three times with ethyl acetate
  13. dry with materialThese extracts were dried over anhydrous sodium sulfate
  14. customevaporated

Sources & evidence

ORD record
ord-3401ae31fb4248d1b5f7e0d8be345509
Source dataset
uspto-grants-1976_01
Patent number
US03933824

Reaction notes

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