1,4-Dibromobenzene → HCID 22128023, compound

HRID 1858599Notes

Reaction equation

HRID 1858599 reaction equation
[Li]CCCC.Br[C:7]1[CH:12]=[CH:11][C:10]([Br:13])=[CH:9][CH:8]=1.[CH2:14]([N:21]1[CH2:26][CH2:25][C:24](=[O:27])[CH2:23][CH2:22]1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[Cl-].[NH4+]>CCCCCC.C(OCC)C>[CH2:14]([N:21]1[CH2:26][CH2:25][CH:24]([OH:27])[CH2:23][CH:22]1[C:7]1[CH:12]=[CH:11][C:10]([Br:13])=[CH:9][CH:8]=1)[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1

Participants

7

Reactant 4

HCID 78041,4-DibromobenzeneHCID 192201-Benzyl-4-piperidoneHCID 25517Ammonium ChlorideHCID 178418339Butyllithium

Product 1

HCID 22128023HCID 22128023, compoundYield 73.2%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
-70 °C

Procedure

400 ml of a 1.2M solution of n-BuLi in hexane were added dropwise within 45 minutes to a solution, cooled to -70° C., of 112.5 g (0.48 mol) of 1,4-dibromobenzene in 1200 ml of diethyl ether in such a manner that the temperature did not rise above -60° C. After completion of the addition the mixture was stirred at -70° C. for 2.5 hours. Thereafter, a solution of 90.84 g (0.48 mol) of 1-benzyl-4-piperidone in 300 ml of ether was added dropwise at -70 to -65° C. during one hour. After the dropwise addition the mixture was stirred at -70° C. for 2 hours. For the working-up, the cold reaction mixture was poured into 1200 ml of a 15% ammonium chloride solution, the mixture was transferred to a separating funnel and the organic phase was separated. The aqueous phase was extracted twice with ether and subsequently the combined organic phases were extracted twice with water and saturated sodium chloride solution. Then, the organic phase was dried over magnesium sulphate evaporated under reduced pressure, with the crude product separating as a yellowish solid. For purification, this was dissolved in hot methylene chloride, the solution was treated with hexane until turbidity began and cooled to room temperature while stirring. The resulting precipitate was filtered off under suction and dried. There were obtained 121.65 g (73% of theory) of 1-benzyl-(4-bromo-phenyl)-piperidin-4-ol as a yellowish solid; m.p.: 106° C., MS: 346, 348 (M+H)+.

Workup

  1. customdid not rise above -60° C
  2. additionAfter completion of the addition the mixture
  3. additionAfter the dropwise addition the mixture
  4. stirringwas stirred at -70° C. for 2 hours
  5. customthe cold reaction mixture
  6. customthe mixture was transferred to a separating funnel
  7. customthe organic phase was separated
  8. extractionThe aqueous phase was extracted twice with ether
  9. extractionsubsequently the combined organic phases were extracted twice with water and saturated sodium chloride solution
  10. dry with materialThen, the organic phase was dried over magnesium sulphate
  11. customevaporated under reduced pressure, with the crude product
  12. customseparating as a yellowish solid
  13. customFor purification
  14. dissolutionthis was dissolved in hot methylene chloride
  15. additionthe solution was treated with hexane until turbidity
  16. temperaturecooled to room temperature
  17. stirringwhile stirring
  18. filtrationThe resulting precipitate was filtered off under suction
  19. customdried

Sources & evidence

ORD record
ord-ccba9b4ef8514605992f3e476991cb66
Source dataset
uspto-grants-2000_11
Patent number
US06150526

Reaction notes

Loading…