Potassium Carbonate → 1-(4-Hydroxyphenyl)-4-(6-phenylpyrid-2-yl)piperazine

HRID 621513

Reaction equation

HRID 621513 reaction equation
Br.Br.[OH:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)=[CH:6][CH:5]=1.Cl[C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[N:18]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[OH:3][C:4]1[CH:5]=[CH:6][C:7]([N:10]2[CH2:15][CH2:14][N:13]([C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([C:23]4[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=4)[N:18]=3)[CH2:12][CH2:11]2)=[CH:8][CH:9]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 2723591p-(1-Piperazinyl)phenol dihydrobromideHCID 27628802-Chloro-6-phenylpyridine

Product 1

HCID 212431781-(4-Hydroxyphenyl)-4-(6-phenylpyrid-2-yl)piperazineYield 22.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 12.77 g (37.5 mmol) of 1-(4-hydroxyphenyl)piperazine dihydrobromide, 7.13 g (37.6 mmol) of 2-chloro-6-phenylpyridine, 8 g (58 mmol) of K2CO3 and 145 ml of absolute DMF were refluxed for 24 hours with stirring. The DMF was then removed by distillation in vacuo. CH2Cl2 /water was added to the residue, the mixture was shaken thoroughly, the phases were separated, and the aqueous solution was extracted repeatedly with CH2Cl2. After drying and filtering, the combined CH2Cl2 extracts were evaporated. The residue was taken up in ethyl acetate, whereupon a crystalline precipitate was produced, which was filtered off under suction. This solid (4.89 g) was a byproduct, to be precise 1-(4-hydroxyphenyl)-4-formylpiperazine. The ethyl acetate solution (filtrate) was evaporated, and the residue remaining (12 g) was chromatographed on a silica gel/CH2Cl2 /petroleum ether 1:2 column (diameter 2.2 cm, height 44 cm). Elution was effected using CH2Cl2 /petroleum ether 1:2, 1:1 and 2:1 mixtures, with CH2Cl2, and with CH2Cl2 /C2H5OH mixtures (0.5-2.0% by volume of C2H5OH). After preliminary fractions, 2.82 g (=22.7% yield) of 1-(4-hydroxyphenyl)-4-(6-phenylpyrid-2-yl)piperazine were obtained as a highly viscous oil;

Workup

  1. temperaturewere refluxed for 24 hours
  2. customThe DMF was then removed by distillation in vacuo
  3. additionCH2Cl2 /water was added to the residue
  4. stirringthe mixture was shaken thoroughly
  5. customthe phases were separated
  6. extractionthe aqueous solution was extracted repeatedly with CH2Cl2
  7. customAfter drying
  8. filtrationfiltering
  9. customthe combined CH2Cl2 extracts were evaporated
  10. customwas produced
  11. filtrationwhich was filtered off under suction
  12. customThe ethyl acetate solution (filtrate) was evaporated
  13. customwas chromatographed on a silica gel/CH2Cl2 /petroleum ether 1:2 column (diameter 2.2 cm, height 44 cm)
  14. washElution

Sources & evidence

ORD record
ord-2de146bfc17d4b5589e971c41852ad2a
Source dataset
uspto-grants-1989_04
Patent number
US04824846

Linked notes

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