Triethylamine → (cis)-1-((4-Chlorophenoxy)methyl)carbonyl-3,5-dimethylpiperazine

HRID 1533070Notes

Reaction equation

HRID 1533070 reaction equation
[CH3:1][C@H:2]1[CH2:7][NH:6][CH2:5][C@@H:4]([CH3:8])[NH:3]1.[Cl:9][C:10]1[CH:20]=[CH:19][C:13]([O:14][CH2:15][C:16](Cl)=[O:17])=[CH:12][CH:11]=1.C(N(CC)CC)C>CO.CCOCC>[Cl:9][C:10]1[CH:20]=[CH:19][C:13]([O:14][CH2:15][C:16]([N:6]2[CH2:5][C@H:4]([CH3:8])[NH:3][C@H:2]([CH3:1])[CH2:7]2)=[O:17])=[CH:12][CH:11]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 77771p-Chlorophenoxyacetyl chlorideHCID 6950261rel-(2R,6S)-2,6-dimethylpiperazine

Product 1

HCID 54020178(cis)-1-((4-Chlorophenoxy)methyl)carbonyl-3,5-dimethylpiperazineYield 80%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 3283Diethyl EtherSolvent

Procedure

To a solution of (cis)-2,6-dimethylpiperazine (0.115 g, 1.1 mmol) in methanol (35 mL) was added 4-chlorophenoxyacetyl chloride (0.205 g, 1.0 mmol, in solution of 6 mL of anhydrous ether). The resulting mixture was stirred at ambient temperature for 10 minutes and then triethylamine (0.10 mL, 0.72 mmol) was added. After 30 minutes, the mixture was concentrated in vacuo to afford an oily residue. This was taken up in ether and washed with saturated aqueous NaHCO3 solution, then brine. The organic layer was separated, dried over MgSO4, filtered and concentrated in vacuo to afford an oil. Purification by flash column chromatography afforded 0.202 g (80% yield) of (cis)-1-((4-chlorophenoxy)methyl)carbonyl-3,5-dimethylpiperazine, a compound of formula (K), as a clear, colorless oil; NMR (CDCl3) 7.3 (d, 2), 6.9 (d, 2), 4.7 (d,1), 4.6 (d,1), 4.4 (d,1), 3.8 (d,1), 2.7 (m, 3), 2.2 (t, 1), 1.1 (m, 6) ppm.

Workup

  1. waitAfter 30 minutes
  2. concentrationthe mixture was concentrated in vacuo
  3. customto afford an oily residue
  4. washwashed with saturated aqueous NaHCO3 solution
  5. customThe organic layer was separated
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto afford an oil
  10. customPurification by flash column chromatography

Sources & evidence

ORD record
ord-f2871ad00e164e618bc6cb883f6087f5
Source dataset
uspto-grants-2001_03
Patent number
US06207665B1

Reaction notes

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