1,4-Dioxane → 2-Piperazineacetic acid, 4-(phenylmethyl)-, methyl ester

HRID 80493Notes

Reaction equation

HRID 80493 reaction equation
[CH2:1]([N:8]([CH2:16][CH2:17][NH:18]C(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[CH2:9]/[CH:10]=[CH:11]/[C:12]([O:14][CH3:15])=[O:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O1CCOCC1>CO>[CH2:1]([N:8]1[CH2:16][CH2:17][NH:18][CH:10]([CH2:11][C:12]([O:14][CH3:15])=[O:13])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 312751,4-DioxaneHCID 67247765(e)-Methyl 4-(benzyl(2-(tritylamino)ethyl)amino)but-2-enoate

Product 1

HCID 156654662-Piperazineacetic acid, 4-(phenylmethyl)-, methyl ester

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of Example 12B (160 g, 326 mmol) in methanol (652 mL) was added 4 MHCl in dioxane (408 mL, 1630 mmol) and the mixture was heated at 50° C. for 3 hours. The solvent was then evaporated and water was added. A solid precipitates. The water layer was decanted and washed once with ethyl acetate. The solid was dissolved in ethyl acetate and extracted with water once. The water layers were combined and treated with 1N NaOH (1 L) until pH=10. The free amine was extracted twice with dichloromethane, dried over sodium sulfate and concentrated to afford the title compound. 1H NMR (500 MHz, DMSO-d6) δ ppm 7.34-7.20 (m, 5H), 3.57 (s, 3H), 3.42 (q, J=13.4 Hz, 2H), 2.96 (qd, J=2.7 Hz, 6.9 Hz, 1H), 2.78 (dt, J=2.9 Hz, 11.9 Hz, 1H), 2.69-2.60 (m, 2H), 2.55 (d, J=10.8 Hz, 1H), 2.30 (dd, J=3.2 Hz, 6.7 Hz, 2H), 1.92 (td, J=2.8 Hz, 10.6 Hz, 1H), 1.68 (t, J=10.0 Hz, 1H); MS (ESI) m/z 249.0 (M+H)+.

Workup

  1. customThe solvent was then evaporated
  2. additionwater was added
  3. customA solid precipitates
  4. customThe water layer was decanted
  5. washwashed once with ethyl acetate
  6. dissolutionThe solid was dissolved in ethyl acetate
  7. extractionextracted with water once
  8. additiontreated with 1N NaOH (1 L) until pH=10
  9. extractionThe free amine was extracted twice with dichloromethane
  10. dry with materialdried over sodium sulfate
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-fdf9a09dd31d42059e859d01e6770858
Source dataset
uspto-grants-2014_09
Patent number
US08846663B2

Reaction notes

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