Dichloromethane → (-)-(2R,5S)-1-allyl-2,5-dimethylpiperazine

HRID 2258356Notes

Reaction equation

HRID 2258356 reaction equation
[CH2:1]([N:4]1[CH2:9][CH:8]([CH3:10])[NH:7][CH2:6][CH:5]1[CH3:11])[CH:2]=[CH2:3].C1(C)C=CC(C([C@](C(O)=O)(O)[C@](C(C2C=CC(C)=CC=2)=O)(O)C(O)=O)=O)=CC=1.[OH-].[Na+].ClCCl>C(O)C>[CH2:1]([N:4]1[CH2:9][C@H:8]([CH3:10])[NH:7][CH2:6][C@H:5]1[CH3:11])[CH:2]=[CH2:3]

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 14798Sodium HydroxideHCID 4135660HCID 4135660, compoundHCID 22860073(2R,3R)-2,3-dihydroxy-2,3-bis(4-methylbenzoyl)butanedioic acid

Product 1

HCID 10534891(-)-(2R,5S)-1-allyl-2,5-dimethylpiperazine

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of racemic 1-allyl-2,5-dimethylpiperazine (3.82 g, 24.8 mmol, Example 42, infra) and (+)-di-p-toluoyl-D-tartaric acid (9.55 g, 24.8 mmol) in absolute ethanol (40 mL) was heated to reflux and allowed to cool gradually to room temperature. After standing for one day the salt was collected by filtration, washed with ethanol and dried to give 11.0 g. This was recrystallized four times from absolute ethanol to give the salt (4.5 g, 68% of theoretical for one enantiomer) as a white solid. The salt (3.3 g, 6.1 mmol) was partitioned between 2N sodium hydroxide solution and dichloromethane. The dichloromethane phase was separated, the alkali washed twice with dichloromethane, and the combined dichloromethane phases were dried with magnesium sulfate and evaporated to give (-)-(2R,5S)-1-allyl-2,5-dimethylpiperazine, (0.92 g, 98% recovery from the salt), [α]D20 =55.7° (ethanol, c=1.8).

Workup

  1. temperaturewas heated
  2. temperatureto reflux
  3. filtrationthe salt was collected by filtration
  4. washwashed with ethanol
  5. customdried
  6. customto give 11.0 g
  7. customThis was recrystallized four times from absolute ethanol
  8. customto give the salt (4.5 g, 68% of theoretical for one enantiomer) as a white solid
  9. customThe dichloromethane phase was separated
  10. washthe alkali washed twice with dichloromethane
  11. dry with materialthe combined dichloromethane phases were dried with magnesium sulfate
  12. customevaporated

Sources & evidence

ORD record
ord-8c01d24681ef48b29e3c93d885ae8b02
Source dataset
uspto-grants-1997_08
Patent number
US05658908

Reaction notes

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