Hydrochloric Acid → trans 2-[4-(1-Oxo-3-phenyl-2-propenyl)-1-piperazinyl]-4,5,6-trimethoxy-1-indanol

HRID 1761637Notes

Reaction equation

HRID 1761637 reaction equation
Br[CH:2]1[CH2:10][C:9]2[C:4](=[CH:5][C:6]([O:15][CH3:16])=[C:7]([O:13][CH3:14])[C:8]=2[O:11][CH3:12])[C:3]1=[O:17].[O:18]=[C:19]([N:28]1[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]1)[CH:20]=[CH:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.C([O-])(O)=O.[Na+].[BH4-].[Na+].Cl>CO.CC(C)=O>[O:18]=[C:19]([N:28]1[CH2:29][CH2:30][N:31]([C@@H:2]2[CH2:10][C:9]3[C:4](=[CH:5][C:6]([O:15][CH3:16])=[C:7]([O:13][CH3:14])[C:8]=3[O:11][CH3:12])[C@H:3]2[OH:17])[CH2:32][CH2:33]1)[CH:20]=[CH:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 2809493-Phenyl-1-(piperazin-1-yl)prop-2-en-1-oneHCID 516892Sodium BicarbonateHCID 4311764Sodium borohydrideHCID 212421392-Bromo-4,5,6-trimethoxy-1-indanone

Product 1

HCID 54307274trans 2-[4-(1-Oxo-3-phenyl-2-propenyl)-1-piperazinyl]-4,5,6-trimethoxy-1-indanolYield 27.4%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 887MethanolSolvent

Procedure

A mixture of 3.3 g (11 mmole) of 2-bromo-4,5,6-trimethoxy-1-indanone (Haworth et al., J. Chem. Soc. 1952 1583-1588), 2.16 g (10 mmole) of 1-(1-oxo-3-phenyl-2-propenyl)-piperazine, 0.92 g (11 mmole) of NaHCO3 in 8 ml of methanol is refluxed with stirring for 16 hours. After cooling, and maintaining the temperature at 0°-5° C., 0.77 g (20 mmole) of NaBH4 are added at portions, then the mixture is allowed to stand for 4 hours at room temperature under stirring. The mixture is cooled and made acidic by the addition of 15% aqueous HCl. After concentration under reduced pressure, the mixture is made alkaline by the addition of an aqueous 5% solution of sodium carbonate and extracted with methylene dichloride. The organic phase is washed with H2O to neutrality and dried over sodium sulfate. On evaporation under reduced pressure, 4.2 g are obtained as a mixture of diastereoisomers cis/trans which are separated by flash-chromatography through a column filled with silicagel 60 Merck 230-400 mesh, using chloroform:acetone 50:50 as the eluent. After crystallization from acetone, 1,2 g of cis-isomer are obtained (yield 27.4%), m.p. 162-163° C. On cristallization from acetone, 1.25 g of trans-isomer are obtained (yield 28.5%); m.p. 168°-170° C.

Workup

  1. temperatureis refluxed
  2. temperatureAfter cooling
  3. temperaturemaintaining the temperature at 0°-5° C.
  4. waitto stand for 4 hours at room temperature
  5. stirringunder stirring
  6. temperatureThe mixture is cooled
  7. concentrationAfter concentration under reduced pressure
  8. additionby the addition of an aqueous 5% solution of sodium carbonate
  9. extractionextracted with methylene dichloride
  10. washThe organic phase is washed with H2O to neutrality
  11. dry with materialdried over sodium sulfate
  12. customOn evaporation under reduced pressure, 4.2 g
  13. customare obtained as a mixture of diastereoisomers cis/trans which
  14. customare separated by flash-chromatography through a column
  15. additionfilled with silicagel 60 Merck 230-400 mesh
  16. customAfter crystallization from acetone, 1,2 g of cis-isomer
  17. customare obtained (yield 27.4%), m.p. 162-163° C

Sources & evidence

ORD record
ord-57858c403cf740c6bf693310b64b60f7
Source dataset
uspto-grants-1989_05
Patent number
US04826975

Reaction notes

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