Hydrochloric Acid → (R)-3-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1040414Notes

Reaction equation

HRID 1040414 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@@H:10]([C:13](=[NH:16])[NH:14][OH:15])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1N=CN([C:22](N2C=NC=C2)=[O:23])C=1.Cl>O1CCOCC1.C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@@H:10]([C:13]2[NH:16][C:22](=[O:23])[O:15][N:14]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 682631,1'-CarbonyldiimidazoleHCID 178452026HCID 178452026, compound

Product 1

HCID 136383477(R)-3-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)-pyrrolidine-1-carboxylic acid tert-butyl esterYield 88.5%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

Crude (R)-3-(N-hydroxycarbamimidoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (887 mg, 3.86 mmol) and CDI (94 mg, 5.8 mmol) were dissolved in dioxane (30 mL) and heated to reflux. After 1 h, the reaction was concentrated in vacuo. The crude reaction mixture was dissolved in CH2Cl2 and the pH was adjusted to 3 by adding 1M HCl to the solution. The layers were separated and the aqueous layer was extracted with CH2Cl2. The combined organic layers were washed with water and brine, dried over MgSO4, filtered and concentrated in vacuo to yield 872 mg of crude (R)-3-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)-pyrrolidine-1-carboxylic acid tert-butyl ester.

Workup

  1. temperatureheated to reflux
  2. concentrationthe reaction was concentrated in vacuo
  3. customThe crude reaction mixture
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted with CH2Cl2
  6. washThe combined organic layers were washed with water and brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-c4702bb5b0e74b46b648f42fd06830f6
Source dataset
uspto-grants-2013_10
Patent number
US08552205B2

Reaction notes

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