Benzylamine → HCID 15023860, compound

HRID 1461046Notes

Reaction equation

HRID 1461046 reaction equation
C(N(CC)CC)C.[F:8][CH2:9][CH:10](O)[CH2:11][N:12]([CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[CH2:13][CH:14](O)[CH2:15][F:16].CS(Cl)(=O)=O.[CH2:31]([NH2:38])[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>O1CCCC1.C(O)C>[CH2:31]([N:38]1[CH:10]([CH2:9][F:8])[CH2:11][N:12]([CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:13][CH:14]1[CH2:15][F:16])[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1

Participants

7

Reactant 4

HCID 7504BenzylamineHCID 8471Triethylamine2×HCID 31297Methanesulfonyl chlorideHCID 18985341HCID 18985341, compound

Product 1

HCID 15023860HCID 15023860, compound

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

28.89 g (0.286 mole) of triethylamine were added to a solution of 33.67 g (0.13 mole) of N,N-bis(3-fluoro-2-hydroxypropyl)benzylamine [prepared as described in step (a) above] in 300 ml of tetrahydrofuran. 32.76 g (0.286 mole) of methanesulfonyl chloride were then added dropwise to the mixture, whilst ice-cooling. After the mixture had been stirred at room temperature for 6 hours, 39.40 g (0.39 mole) of triethylamine, 20.87 g (0.195 mole) of benzylamine and 300 ml of ethanol were added to it, and it was then heated under reflux for 3 hours. At the end of this time, the reaction mixture was concentrated by evaporation under reduced pressure, and 300 ml of water containing 30 g of sodium hydroxide were added to the residue. The aqueous mixture thus obtained was extracted with ethyl acetate and the organic extracts were washed with water, dried over anhydous sodium sulfate and concentrated by evaporation under reduced pressure. The residue was purified by column chromatography through silica gel using a 20:1 by volume mixture of toluene and ethyl acetate as the eluent, to afford 1,4-dibenzyl-2,6-bis(fluoromethyl)piperazine, including 6.29 g of isomer A and 6.60 g of isomer B, as colorless crystals.

Workup

  1. temperaturecooling
  2. temperaturewas then heated
  3. temperatureunder reflux for 3 hours
  4. concentrationAt the end of this time, the reaction mixture was concentrated by evaporation under reduced pressure, and 300 ml of water containing 30 g of sodium hydroxide
  5. additionwere added to the residue
  6. customThe aqueous mixture thus obtained
  7. extractionwas extracted with ethyl acetate
  8. washthe organic extracts were washed with water
  9. dry with materialdried over anhydous sodium sulfate
  10. concentrationconcentrated by evaporation under reduced pressure
  11. customThe residue was purified by column chromatography through silica gel using a 20:1
  12. additionby volume mixture of toluene and ethyl acetate as the eluent

Sources & evidence

ORD record
ord-6fb13175225f48b5a940e3533d7380ad
Source dataset
uspto-grants-1991_12
Patent number
US05073556

Reaction notes

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