Acetoxyacetyl chloride → 1,1-Dimethylethyl 4-{5-[(acetoxy)methyl]-1,2,4-oxadiazol-3-yl}piperazine-1-carboxylate

HRID 244575Notes

Reaction equation

HRID 244575 reaction equation
[OH:1][NH:2][C:3](=[NH:17])[N:4]1[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:6][CH2:5]1.C(N(C(C)C)CC)(C)C.[C:27]([O:30][CH2:31][C:32](Cl)=O)(=[O:29])[CH3:28]>C1COCC1.O>[C:27]([O:30][CH2:31][C:32]1[O:1][N:2]=[C:3]([N:4]2[CH2:5][CH2:6][N:7]([C:10]([O:12][C:13]([CH3:14])([CH3:16])[CH3:15])=[O:11])[CH2:8][CH2:9]2)[N:17]=1)(=[O:29])[CH3:28]

Participants

6

Reactant 3

HCID 26297Acetoxyacetyl chlorideHCID 81531DiisopropylethylamineHCID 178452346tert-butyl 4-(N-hydroxyamidino)-piperazine-1-carboxylate

Product 1

HCID 668385551,1-Dimethylethyl 4-{5-[(acetoxy)methyl]-1,2,4-oxadiazol-3-yl}piperazine-1-carboxylateYield 76%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

1,1-Dimethylethyl 4-[(hydroxyamino)(imino)methyl]piperazine-1-carboxylate (3.58 g, 14.6 mmol) was suspended in THF (50 mL) followed by the addition of diisopropylethylamine (3.0 mL, 17.5 mmol) and the mixture was cooled to 0° C. Acetoxyacetyl chloride (1.6 mL, 14.6 mmol) was added by syringe and the mixture was allowed to stir an additional 30 minutes at 0° C. The resulting homogeneous solution was allowed to warm to room temperature then concentrated in vacuo to afford a white solid residue. The material was suspended in water (50 ml) and the solid product was collected by filtration, washed with additional water then hexanes and dried in vacuo. The intermediate O-acyl derivative was then suspended in THF (50 mL) followed by addition of TBAF (1.0M in THF, 3.5 mL) and the mixture was stirred for 30 minutes at room temperature. The homogeneous solution obtained was concentrated in vacuo and the residue partitioned with ethyl ether and water. The organic layer was washed twice with additional water then with saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate. Filtration and concentration gave 1,1-dimethylethyl 4-{5-[(acetoxy)methyl]-1,2,4-oxadiazol-3-yl}piperazine-1-carboxylate (3.6 g, 76% yield) as a colorless crystalline solid. 1H-NMR (400 MHz, CDCl3): 5.14 (s, 2H), 3.51 (tr, 4H), 3.42 (tr, 4H), 2.18 (s, 3H), 1.48 (s, 9H).

Workup

  1. temperatureto warm to room temperature
  2. concentrationthen concentrated in vacuo
  3. customto afford a white solid residue
  4. filtrationthe solid product was collected by filtration
  5. washwashed with additional water
  6. dry with materialhexanes and dried in vacuo
  7. additionfollowed by addition of TBAF (1.0M in THF, 3.5 mL)
  8. stirringthe mixture was stirred for 30 minutes at room temperature
  9. customThe homogeneous solution obtained
  10. concentrationwas concentrated in vacuo
  11. customthe residue partitioned with ethyl ether and water
  12. washThe organic layer was washed twice with additional water
  13. dry with materialwith saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate
  14. filtrationFiltration and concentration

Sources & evidence

ORD record
ord-52098b4a18e44965ba628b168df84a1b
Source dataset
uspto-grants-2014_02
Patent number
US08658654B2

Reaction notes

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