Acetic Acid → 1-Benzyl 4-tert-butyl 2-methyl piperazine-1,2,4-tricarboxylate

HRID 1598484Notes

Reaction equation

HRID 1598484 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH:12]1[C:24]([OH:26])=[O:25])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:27][Si](C=[N+]=[N-])(C)C.C(O)(=O)C>CO.C1C=CC=CC=1.CCCCCC>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:22])([CH3:23])[CH3:21])=[O:18])[CH2:13][CH:12]1[C:24]([O:26][CH3:27])=[O:25])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 3

HCID 176Acetic AcidHCID 167693TrimethylsilyldiazomethaneHCID 2756777N-4-Boc-N-1-Cbz-2-piperazine carboxylic acid

Product 1

HCID 44519651-Benzyl 4-tert-butyl 2-methyl piperazine-1,2,4-tricarboxylate

Reagents, catalysts & solvents 3

HCID 241BenzeneSolventHCID 887MethanolSolventHCID 8058HexaneSolvent

Procedure

1-Benzyloxycarbonyl-4-tert-butoxycarbonyl-piperazine-2-carboxylic acid (4.76 g, 13.0 mmol) (prepared as described by C. F. Bigge, S. J. Hays, P. M. Novak, J. T. Drummond, G. Johnson, T. P. Bobovski in Tetrahedron Letters, Vol. 30, 5193-5196, 1989) was dissolved in 10% methanol in benzene. A solution of trimethylsilyldiazomethane in hexane (8 mL, 2M) was added dropwise. After 10 min, glacial acetic acid (1 mL) was added. When gas evolution ceased, the solvents were removed in vacuo, and the residue partitioned between ethyl acetate and saturated sodium bicarbonate. The organic phase was washed with saturated brine and dried over magnesium sulfate. The crude product was chromatographed on silica gel with 15% ethyl acetate in hexane, then recrystallized from ethyl acetate/hexane to obtain the title compound as a white powder (1.8 g).

Workup

  1. customthe solvents were removed in vacuo
  2. customthe residue partitioned between ethyl acetate and saturated sodium bicarbonate
  3. washThe organic phase was washed with saturated brine
  4. dry with materialdried over magnesium sulfate
  5. customThe crude product was chromatographed on silica gel with 15% ethyl acetate in hexane
  6. customrecrystallized from ethyl acetate/hexane

Sources & evidence

ORD record
ord-e8c2fc9d0c6245f087446bcc0d508dc4
Source dataset
uspto-grants-1998_04
Patent number
US05736539

Reaction notes

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