Acetic Acid → 3,4,5-Trimethyl-piperazine-1-carboxylic acid benzyl ester

HRID 1798550Notes

Reaction equation

HRID 1798550 reaction equation
[CH3:1][CH:2]1[NH:7][CH:6]([CH3:8])[CH2:5][N:4]([C:9]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:10])[CH2:3]1.C=O.[C:21](O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CO>[CH2:12]([O:11][C:9]([N:4]1[CH2:3][CH:2]([CH3:1])[N:7]([CH3:21])[CH:6]([CH3:8])[CH2:5]1)=[O:10])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 23078633Benzyl 3,5-dimethylpiperazine-1-carboxylate

Product 1

HCID 687346163,4,5-Trimethyl-piperazine-1-carboxylic acid benzyl ester

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Benzyl 3,5-dimethylpiperazine-1-carboxylate (1 eq, 2.04 mmol, 0.5 g) and formaldehyde (37% in H2O, 5 eq, 10.07 mmol, 0.277 ml) are dissolved in MeOH (10 ml). After 10 mins at room temperature, acetic acid (5 eq, 10.07 mmol, 0.576 ml) and sodium triacetoxyborohydride (5 eq, 10.07 mmol, 2.13 g) are added and the reaction mixture stirred overnight. The reaction is quenched with 5M HCl (15 ml) and the solvent evaporated under vacuo. The residue is taken to pH 13 by addition of sodium hydroxide (4M) and extracted with EtOAc. This organic portion is washed with water and brine, dried over MgSO4, filtered and concentrated in vacuo to afford the title compound.

Workup

  1. customThe reaction is quenched with 5M HCl (15 ml)
  2. customthe solvent evaporated under vacuo
  3. additionThe residue is taken to pH 13 by addition of sodium hydroxide (4M)
  4. extractionextracted with EtOAc
  5. washThis organic portion is washed with water and brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-5d93b66ab1ef41348e1c8fa5d822851d
Source dataset
uspto-grants-2013_01
Patent number
US08343966B2

Reaction notes

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