Tetrahydrofuran → HCID 13588995, compound

HRID 648946Notes

Reaction equation

HRID 648946 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][C:11](=[O:14])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl-:15].[NH4+:16].O1[CH2:21][CH2:20][CH2:19][CH2:18]1>>[ClH:15].[CH2:1]([N:8]1[CH2:13][CH2:12][C:11]([C:18]2[CH:9]=[CH:10][CH:11]=[C:12]3[C:19]=2[CH:20]=[CH:21][N:16]3[CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)([OH:14])[CH2:10][CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 192201-Benzyl-4-piperidoneHCID 25517Ammonium Chloride

Product 1

HCID 13588995HCID 13588995, compound

Procedure

9 g of magnesium and 24.2 g of N-benzyl-4-chloro-indole were reacted as in stage A of Example 1 of French Patent No. 2,458,549 to form the magnesium derivative of N-benzyl-4-chloro-indol. A solution of 17.7 g of N-benzyl-4-piperidinone in 40 ml of tetrahydrofuran were introduced into the acid solution at 30° C. while keeping the temperature below 40° C. The mixture was refluxed for 2 hours and then was cooled to 10° C. after which an aqueous saturated ammonium chloride solution was added thereto. The mixture was filtered to remove excess magnesium and the filtrate was extracted with ethyl acetate. The organic phase was washed with aqueous sodium hydroxide, was dried and evaporated to dryness under reduced pressure. The 42 g of brown oil residue were dissolved in 400 ml of ethyl acetate and a saturated solution of hydrogen chloride in ethyl acetate was added thereto. The mixture was filtered and the product was dried under reduced pressure and crystallized from an isopropanol-methanol mixture to obtain 17.3 g of 1-benzyl-4-[1-benzyl-1H-indole-4 -yl]-4-piperidinol hydrochloride with a melting point of 270° C. The free base was obtained by treatment of the salt with sodium hydroxide, extraction with ethyl acetate and evaporation of the organic phase.

Workup

  1. customthe temperature below 40° C
  2. temperatureThe mixture was refluxed for 2 hours
  3. additionwas added
  4. filtrationThe mixture was filtered
  5. customto remove excess magnesium
  6. extractionthe filtrate was extracted with ethyl acetate
  7. washThe organic phase was washed with aqueous sodium hydroxide
  8. customwas dried
  9. customevaporated to dryness under reduced pressure
  10. dissolutionThe 42 g of brown oil residue were dissolved in 400 ml of ethyl acetate
  11. additiona saturated solution of hydrogen chloride in ethyl acetate was added
  12. filtrationThe mixture was filtered
  13. customthe product was dried under reduced pressure
  14. customcrystallized from an isopropanol-methanol mixture

Sources & evidence

ORD record
ord-ae71f25f729b46d2b3d7ff83726d6558
Source dataset
uspto-grants-1988_04
Patent number
US04737505

Reaction notes

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