Piperidine → 4-(2-Piperidinoethyl)-1-bromobenzene

HRID 1505906Notes

Reaction equation

HRID 1505906 reaction equation
CS(Cl)(=O)=O.[Br:6][C:7]1[CH:12]=[CH:11][C:10]([CH2:13][CH2:14]O)=[CH:9][CH:8]=1.C(N(CC)CC)C.[NH:23]1[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1.C(=O)([O-])[O-].[K+].[K+]>C(Cl)Cl.C(#N)C>[Br:6][C:7]1[CH:12]=[CH:11][C:10]([CH2:13][CH2:14][N:23]2[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]2)=[CH:9][CH:8]=1

Participants

8

Reactant 5

HCID 8082PiperidineHCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 728512-(4-Bromophenyl)ethanol

Product 1

HCID 121778074-(2-Piperidinoethyl)-1-bromobenzeneYield 95.3%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Methanesulfonyl chloride (0.43 mL, 5.47 mmol) was added to a solution of 2-(4-bromophenyl)-ethanol (1.0 g, 4.97 mmol) and triethylamine (0.84 mL, 5.96 mmol) in DCM (20 mL) at 0° C. The reaction mixture was stirred at 0° C. for 15 minutes then at ambient temperature for 2 h. The reaction mixture was partitioned between water and DCM and the organic phase was dried over sodium sulfate, filtered and evaporated to give a colourless oil. The resultant residue was dissolved in acetonitrile (10 mL), piperidine (0.491 mL, 4.97 mmol) and potassium carbonate (0.823 g, 5.96 mmol) were added and the reaction mixture was heated at 70° C. for 2.5 h. The reaction mixture was allowed to cool to ambient temperature then partitioned between ethyl acetate and water. The organic phase was dried over sodium sulfate, filtered and evaporated and the resultant residue dissolved in methanol and loaded onto a 10 g SCX-2 cartridge. The column was washed with methanol then eluted with 2N ammonia in methanol and the basic fractions were evaporated to afford the title compound (1.27 g, 95%) as a colourless oil. 1H NMR (CDCl3, 300 MHz): 7.41-7.36 (m, 2H), 7.10-7.04 (m, 2H), 2.79-2.71 (m, 2H), 2.54-2.40 (m, 6H), 1.66-1.56 (m, 4H), 1.50-1.40 (m, 2H).

Workup

  1. waitat ambient temperature for 2 h
  2. customThe reaction mixture was partitioned between water and DCM
  3. dry with materialthe organic phase was dried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated
  6. customto give a colourless oil
  7. temperaturethe reaction mixture was heated at 70° C. for 2.5 h
  8. temperatureto cool to ambient temperature
  9. customthen partitioned between ethyl acetate and water
  10. dry with materialThe organic phase was dried over sodium sulfate
  11. filtrationfiltered
  12. customevaporated
  13. dissolutionthe resultant residue dissolved in methanol
  14. washThe column was washed with methanol
  15. washthen eluted with 2N ammonia in methanol
  16. customthe basic fractions were evaporated

Sources & evidence

ORD record
ord-c30444aefacc4dad8a2f3e97bb219013
Source dataset
uspto-grants-2015_12
Patent number
US09216980B2

Reaction notes

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