Benzathine → Methyl 2-(1,4-dibenzylpiperazin-2-yl)acetate

HRID 1061052Notes

Reaction equation

HRID 1061052 reaction equation
Br/[C:2](/[CH3:8])=[CH:3]\[C:4]([O:6][CH3:7])=[O:5].[CH2:9]([NH:16][CH2:17][CH2:18][NH:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1>C1(C)C=CC=CC=1.C(N(CC)CC)C>[CH2:9]([N:16]1[CH2:17][CH2:18][N:19]([CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH2:8][CH:2]1[CH2:3][C:4]([O:6][CH3:7])=[O:5])[C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1

Participants

5

Reactant 2

HCID 8793BenzathineHCID 12625788Methyl 3-bromocrotonate

Product 1

HCID 22710010Methyl 2-(1,4-dibenzylpiperazin-2-yl)acetate

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8471TriethylamineSolvent2×

Procedure

In toluene (250 ml), N,N′-dibenzylethylenediamine (12 ml) and triethylamine (12 ml) were dissolved, followed by the dropwise addition of methyl 3-bromocrotonate (7.0 ml) under ice cooling. The resulting mixture was stirred at room temperature for 24 hours. After the addition of triethylamine (2.0 ml), the resulting mixture was stirred at room temperature for 71 hours. The insoluble matter was filtered off and the filtrate was distilled under reduced pressure. The residue was added with 10% hydrochloric acid (300 ml) and crystals so precipitated were removed by filtration. Ethyl acetate was added to the filtrate. Potassium carbonate was added to the water layer so separated to make it alkaline. Ethyl acetate was added to the resulting mixture. The organic layer so separated was washed with saturated saline and dried over anhydrous potassium carbonate. The solvent was then distilled off under reduced pressure. The residue was purified by chromatography on a silica gel column (hexane:ethyl acetate=4:1), whereby the title compound (1.07 g, 62%) was obtained.

Workup

  1. stirringthe resulting mixture was stirred at room temperature for 71 hours
  2. filtrationThe insoluble matter was filtered off
  3. distillationthe filtrate was distilled under reduced pressure
  4. additionThe residue was added with 10% hydrochloric acid (300 ml) and crystals
  5. customso precipitated
  6. customwere removed by filtration
  7. additionEthyl acetate was added to the filtrate
  8. additionPotassium carbonate was added to the water layer
  9. customso separated
  10. additionEthyl acetate was added to the resulting mixture
  11. customThe organic layer so separated
  12. washwas washed with saturated saline
  13. dry with materialdried over anhydrous potassium carbonate
  14. distillationThe solvent was then distilled off under reduced pressure
  15. customThe residue was purified by chromatography on a silica gel column (hexane:ethyl acetate=4:1), whereby the title compound (1.07 g, 62%)
  16. customwas obtained

Sources & evidence

ORD record
ord-e507016c3b1d40aba010a7a0460f0960
Source dataset
uspto-grants-2003_02
Patent number
US06525042B1

Reaction notes

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