Tetrahydrofuran → 3-Piperidinone, 1-(phenylmethyl)-

HRID 1155680Notes

Reaction equation

HRID 1155680 reaction equation
[Mg:1].Cl[C:3]1[CH:11]=[CH:10][CH:9]=[C:8]2C=1C=C[N:7]2[CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[O:19]1CCCC1>BrCCBr>[Mg:1].[CH2:12]([N:7]1[CH2:3][CH2:11][CH2:10][C:9](=[O:19])[CH2:8]1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

6

Reactant 3

HCID 8028Tetrahydrofuran3×HCID 5462224MagnesiumHCID 12900681HCID 12900681, compound

Product 2

HCID 966503-Piperidinone, 1-(phenylmethyl)-HCID 5462224Magnesium

Reagents, catalysts & solvents 1

HCID 78391,2-DibromoethaneSolvent

Conditions

Temperature
30 °C

Procedure

A mixture of 113 g of magnesium in 200 ml of tetrahydrofuran was refluxed while a solution of 184 g of the product of Step A in 20 ml of 1,2-dibromoethane and 300 ml of tetrahydrofuran were added slowly thereto and the mixture was then refluxed for 3 hours and cooled to 30° C. to obtain a magnesium solution to which a solution of 128 g of N-benzyl-3-piperidone in 250 ml of tetrahydrofuran was added while keeping the temperature below 35° C. The mixture was refluxed for 2 hours and then was cooled to 20° C. Then one liter of an aqueous saturated ammonium chloride solution was slowly added thereto and 2 liters of ethyl acetate were added thereto. The mixture was filtered and the decanted ethyl acetate phase was washed with water, dried and evaporated to dryness. The 330 g of residue were chromatographed over silica gel and were eluted with a 9-1 cyclohexane-triethylamine mixture to obtain 218.4 g of product which was dissolved in ethyl acetate. The solution was extracted with 1 N hydrochloric acid and the aqueous phase was made alkaline by addition of ammonium hydroxide. The mixture was extracted with ethyl acetate and the organic phase was dried. 100 ml of ethyl acetate saturated with gaseous hydrogen chloride were added to the organic phase and the mixture was filtered. The recovered product was washed with ethyl acetate, with ether and dried to obtain 194 g of 1-benzyl-3-[1-benzyl-1H-indole-4 -yl]-3-piperidinol hydrochloride melting at 185° C. Crystallization from ethyl acetate containing 10% methanol yielded the pure product melting at 190° C. The free base was obtained by treating the hydrochloride salt with sodium hydroxide, extracting the aqueous phase with ethyl acetate and evaporating the organic phase to dryness.

Workup

  1. additionwere added slowly
  2. temperaturethe mixture was then refluxed for 3 hours

Sources & evidence

ORD record
ord-020c6d9de8e84a8d891f46c67c5972a1
Source dataset
uspto-grants-1982_06
Patent number
US04332808

Reaction notes

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