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

HRID 1186216Notes

Reaction equation

HRID 1186216 reaction equation
Br[CH2:2]/[CH:3]=[CH:4]/[C:5]([O:7][CH3:8])=[O:6].C(N(CC)CC)C.[CH2:16]([NH:23][CH2:24][CH2:25][NH:26][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>C1(C)C=CC=CC=1>[CH2:16]([N:23]1[CH2:24][CH2:25][N:26]([CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH2:2][CH:3]1[CH2:4][C:5]([O:7][CH3:8])=[O:6])[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 8793BenzathineHCID 53691752-Butenoic acid, 4-bromo-, methyl ester

Product 1

HCID 22710010Methyl 2-(1,4-dibenzylpiperazin-2-yl)acetateYield 72.2%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Methyl 4-bromocrotonate (Aldrich, 5.53 mL, 40 mmol) was added dropwise with stirring to an ice-cooled solution of triethylamine (11.15 mL, 80 mmol) and N,N′-dibenzylethylenediamine (Aldrich, 9.67 mL, 40 mmol) in toluene (200 mL). The solution was stirred with ice cooling for 1 hour, then allowed to warm gradually to room temperature and stirred 25 hours longer. The mixture was filtered through a pad of diatomaceous earth with an ethyl acetate (20 mL) rinse. The filtrate was concentrated to an oil, which was mixed with 10% aqueous HCl (240 mL). After 5 minutes, the mixture was filtered and the cake was rinsed with water (2×10 mL). The filtrate was washed with ethyl acetate (2×80 mL) and the aqueous phase was made basic (pH˜9-10) by portionwise addition of solid K2CO3 (26 g), then 25% aqueous NaOH (10 mL). The turbid mixture was extracted with ethyl acetate (3×120 mL) and the combined extracts were washed with brine (100 mL), dried (MgSO4) and concentrated under vacuum to leave the title compound as an oil (9.78 g): 1H NMR (300 MHz, CDCl3) δ ppm 2.30-2.47 (m, 4H), 2.49-2.73 (m, 4H), 3.06-3.18 (m, 1H), 3.43 (d, J=13.2 Hz, 2H), 3.53 (d, J=13.2 Hz, 1H), 3.60 (s, 3H), 3.76 (d, J=13.6 Hz, 1H), 7.14-7.36 (m, 10H); MS (DCI) m/z 339 (M+H)+.

Workup

  1. stirringstirred 25 hours longer
  2. filtrationThe mixture was filtered through a pad of diatomaceous earth with an ethyl acetate (20 mL)
  3. washrinse
  4. concentrationThe filtrate was concentrated to an oil, which
  5. additionwas mixed with 10% aqueous HCl (240 mL)
  6. waitAfter 5 minutes
  7. filtrationthe mixture was filtered
  8. washthe cake was rinsed with water (2×10 mL)
  9. washThe filtrate was washed with ethyl acetate (2×80 mL)
  10. additionby portionwise addition of solid K2CO3 (26 g)
  11. extractionThe turbid mixture was extracted with ethyl acetate (3×120 mL)
  12. washthe combined extracts were washed with brine (100 mL)
  13. dry with materialdried (MgSO4)
  14. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-080fa989c1604d00bc094622c784cd7f
Source dataset
uspto-grants-2014_03
Patent number
US08673896B2

Reaction notes

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