Diethyl Ether → 1-(4-(1-Hydroxy-1-methylethyl)phenyl)4-(4-pyridyl)piperazine

HRID 427464Notes

Reaction equation

HRID 427464 reaction equation
[CH2:1]([Mg]Cl)C.[C:5]([C:8]1[CH:13]=[CH:12][C:11]([N:14]2[CH2:19][CH2:18][N:17]([C:20]3[CH:25]=[CH:24][N:23]=[CH:22][CH:21]=3)[CH2:16][CH2:15]2)=[CH:10][CH:9]=1)(=[O:7])[CH3:6].C(OCC)C.[Cl-].[NH4+]>C1COCC1>[OH:7][C:5]([C:8]1[CH:9]=[CH:10][C:11]([N:14]2[CH2:15][CH2:16][N:17]([C:20]3[CH:25]=[CH:24][N:23]=[CH:22][CH:21]=3)[CH2:18][CH2:19]2)=[CH:12][CH:13]=1)([CH3:1])[CH3:6]

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 25517Ammonium ChlorideHCID 183571351-(4-Acetylphenyl)-4-(4-pyridyl)piperazineHCID 178461633HCID 178461633, compound

Product 1

HCID 183570461-(4-(1-Hydroxy-1-methylethyl)phenyl)4-(4-pyridyl)piperazineYield 21%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
70 °C

Procedure

Ethyl magnesium chloride (3M) in anhydrous THF (10 ml) was treated at room temperature under argon with a solution of 1-(4-acetylphenyl)-4-(4-pyridyl)piperazine (281 mg) in anhydrous THF (15 ml). The resulting solid suspension was heated at 70° C. under reflux for 3 hours. The mixture was cooled in ice at 0-5° C. and treated with diethyl ether and a saturated solution of aqueous ammonium chloride. The reaction mixture was stirred for 10 minutes with ice cooling and at room temperature for 10 minutes. The aqueous phase was then extracted with dichloromethane and the ether phase was evaporated. The residue was dissolved in dichloromethane and combined with the other organic extracts. The combined extracts were then washed with saturated brine, dried over MgSO4, filtered and evaporated to give an impure orange solid. The solid was purified by chromatography on a prepacked silica column (“Varian bond elut-trademark), eluting with a mixture of methanol (1-2%) and ammonium hydroxide (1%) in dichloromethane to obtain a pale yellow solid which was triturated with diethyl ether to give 1-(4-(1-hydroxy-1-methylethyl)phenyl)4-(4-pyridyl)piperazine (21% yield) as a pale yellow solid, m.p. 234-235° C.

Workup

  1. temperatureunder reflux for 3 hours
  2. temperatureThe mixture was cooled in ice at 0-5° C.
  3. extractionThe aqueous phase was then extracted with dichloromethane
  4. customthe ether phase was evaporated
  5. dissolutionThe residue was dissolved in dichloromethane
  6. washThe combined extracts were then washed with saturated brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. customevaporated
  10. customto give an impure orange solid
  11. customThe solid was purified by chromatography on a prepacked silica column (“Varian bond elut-trademark)
  12. washeluting with a mixture of methanol (1-2%) and ammonium hydroxide (1%) in dichloromethane
  13. customto obtain a pale yellow solid which
  14. customwas triturated with diethyl ether

Sources & evidence

ORD record
ord-5ffee672183d4c1a9834844ff0b39d89
Source dataset
uspto-grants-2001_11
Patent number
US06313127B1

Reaction notes

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