Ozone → 6-methoxy-piperazine-1,2,4-tricarboxylic Acid 4-benzyl Ester 1-tert-butyl Ester 2-methyl Ester

HRID 722719Notes

Reaction equation

HRID 722719 reaction equation
[CH3:1][O:2][C:3](=[O:28])[C@@H:4]([NH:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:5][N:6]([CH2:17][CH:18]=C)[C:7]([O:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:8].O=[O+][O-].C(Cl)Cl.[CH3:35][OH:36]>CO>[CH3:1][O:2][C:3]([CH:4]1[CH2:5][N:6]([C:7]([O:9][CH2:10][C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=2)=[O:8])[CH2:17][CH:18]([O:36][CH3:35])[N:20]1[C:21]([O:23][C:24]([CH3:27])([CH3:25])[CH3:26])=[O:22])=[O:28]

Participants

5

Reactant 3

HCID 24823OzoneHCID 21226129Dichloromethane methanolHCID 69660276HCID 69660276, compound

Product 1

HCID 696600436-methoxy-piperazine-1,2,4-tricarboxylic Acid 4-benzyl Ester 1-tert-butyl Ester 2-methyl EsterYield 53%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
-78 °C

Procedure

A solution containing 3-(allylbenzyloxycarbonylamino)-2-(S)-tert-butoxycarbonylamino propionic acid methyl ester (5.2 g, 12.8 mmol) in 550 mL of 10:1 CH2Cl2/MeOH is cooled to −78° C. Ozone gas is passed through the solution until a blue color persists. The solution is purged with N2 to remove excess ozone and is then treated with excess dimethylsulfide. The solution is allowed to warm to rt overnight and the next morning concentrated in vacuo. The crude residue obtained is re-dissolved in MeOH and treated with Dowex50x-200. After stirring for 4 h, the solution was filtered, concentrated and immediately purified by flash chromatography on silica gel (EtOAc/hexane) to afford 2.75 g (53% yield) of the desired product. 1H NMR (CDCl3) δ 7.40 (m, 5H), 5.60–3.40 (series of m, 6H), 5.19 (br s, 2H), 3.74 (s, 3H), 3.40 (series of s, 3H), 1.50 (series of s, 9H); MS 409 (M+H)+.

Workup

  1. customThe solution is purged with N2
  2. customto remove excess ozone
  3. additionis then treated with excess dimethylsulfide
  4. temperatureto warm to rt overnight
  5. concentrationthe next morning concentrated in vacuo
  6. customThe crude residue obtained
  7. additiontreated with Dowex50x-200
  8. filtrationthe solution was filtered
  9. concentrationconcentrated
  10. customimmediately purified by flash chromatography on silica gel (EtOAc/hexane)

Sources & evidence

ORD record
ord-3d97566faee64db5a5edfc000fb2d3d9
Source dataset
uspto-grants-2006_11
Patent number
US07138395B2

Reaction notes

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