1H-Indole, 6-methyl- → 6-methyl-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole

HRID 2209996Notes

Reaction equation

HRID 2209996 reaction equation
[K].Cl.O.[NH:4]1[CH2:9][CH2:8][C:7](=O)[CH2:6][CH2:5]1.[CH3:11][C:12]1[CH:20]=[C:19]2[C:15]([CH:16]=[CH:17][NH:18]2)=[CH:14][CH:13]=1>CO>[CH3:11][C:12]1[CH:20]=[C:19]2[C:15]([C:16]([C:7]3[CH2:6][CH2:5][NH:4][CH2:9][CH:8]=3)=[CH:17][NH:18]2)=[CH:14][CH:13]=1

Participants

5

Reactant 3

HCID 1379281H-Indole, 6-methyl-HCID 2723901PiperonylamineHCID 5462222Potassium

Product 1

HCID 104207266-methyl-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indoleYield 92.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

To a solution of potassium hydroxyde (16 g) in methanol were added at 5° C. 4-piperidone hydrate hydrochloride (30 g) and a solution of 6-methyl-1H-indole (10 g) in methanol (50 ml). The mixture was refluxed for 16 hours. After cooling precipitated inorganic salts were filtered off. Methanol was evaporated and the remaining oil was dissolved in ethyl acetate (200 ml) and subsequently washed with brine (2×100 ml). After drying (anh. MgSO4) the solvent was evaporated leaving 15 g of crude 6-methyl-3-(1,2,3,6-tetrahydro-4-pyridyl)-1H-indole, which was used without further purification. The pure tetrahydropyridyl derivative crystallized from diethyl ether. Mp: 150°-152° C. To a solution of 1-(2-chloroethyl)-3-(2-propyl)-2-imidazolidinon (32 g)in MIBK (500 ml) were added 6-methyl-3-(1,2,3,6-tetrahydro-4-pyridyl)-1H-indole (15 g), potassium carbonate (16 g) and potassium iodide (5 g). The mixture was refluxed for 19 hours and finally filtered while still hot. MIBK was evaporated and the resulting oil was dissolved in ethyl acetate (500 ml) and washed with brine (2×100 ml). After drying (anh. Na2SO4) ethyl acetate was evaporated. The remaining oil was stirred with diethyl ether (200 ml) and the precipitated, crystalline 3-[1-[2-[3-(2-propyl)-2-imidazolidinon-1-yl]ethyl]-1,2,3,6-tetrahydro-4-pyridyl]-6-methyl-1H-indole was filtered off. Yield: 14.5 g. Mp: 170°-174° C. To a solution of the thus prepared imidazolidinon derivative (14 g) in acetic acid (300 ml) was added PtO2 (600 mg). This mixture was hydrogenated in a Parr apparatus at 3 ato. for 72 hours. The catalyst was filtered off and most of the acetic acid was evaporated in vacuo. The remaining oil was dissolved in H2O and pH was adjusted to 9-10 by addition of dil. NaOH solution. The title compound 14a was extracted with dichloromethane (2×200 ml) and isolated as above. The crude product was purified by eluting (eluent:ethyl acetate/dichloromethane/ethanol/triethyla-mine 40:40:20:5) through silica gel. Yield: 4.5 g. Mp: 185° C.

Workup

  1. temperatureThe mixture was refluxed for 16 hours
  2. temperatureAfter cooling
  3. customprecipitated inorganic salts
  4. filtrationwere filtered off
  5. customMethanol was evaporated
  6. dissolutionthe remaining oil was dissolved in ethyl acetate (200 ml)
  7. washsubsequently washed with brine (2×100 ml)
  8. dry with materialAfter drying (anh. MgSO4) the solvent
  9. customwas evaporated

Sources & evidence

ORD record
ord-d3e557b88d3e4932afa52508cd6d81d4
Source dataset
uspto-grants-1995_10
Patent number
US05457115

Reaction notes

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