1,1'-Carbonyldiimidazole → (1-(5-Oxo-4,5-dihydro-[1,2,4]oxadiazol-3-yl)-spiro[2.5]oct-1-ylmethyl]-carbamic acid tert-butyl ester

HRID 1297229Notes

Reaction equation

HRID 1297229 reaction equation
[C:1]([O:5][C:6](=[O:21])[NH:7][CH2:8][C:9]1([C:17](=[NH:20])[NH:18][OH:19])[C:11]2([CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]2)[CH2:10]1)([CH3:4])([CH3:3])[CH3:2].C1N=CN([C:27](N2C=NC=C2)=[O:28])C=1>C1COCC1>[C:1]([O:5][C:6](=[O:21])[NH:7][CH2:8][C:9]1([C:17]2[NH:20][C:27](=[O:28])[O:19][N:18]=2)[C:11]2([CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]2)[CH2:10]1)([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 682631,1'-Carbonyldiimidazole2×HCID 178453109HCID 178453109, compound

Product 1

HCID 136338587(1-(5-Oxo-4,5-dihydro-[1,2,4]oxadiazol-3-yl)-spiro[2.5]oct-1-ylmethyl]-carbamic acid tert-butyl esterYield 70%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of [1-(N-hydroxycarbamimidoyl)-spiro[2.5]oct-1-ylmethyl]-carbamic acid tert-butyl ester (5.8 g, 19.5 mmol) in THF (250 mL) was added CDI (4.74 g, 29.3 mmol). After 3 hours at reflux another portion of CDI (1 g) was added. The solution was heated to reflux for an additional 4 hours and then the solvent was removed under reduced pressure. The residue was partitioned between ether (200 mL) and 1N NaOH (75 mL). The organic layer was extracted with 1N NaOH (2×75 mL). The combined aqueous layers were washed with ether (100 mL). The aqueous layer was acidified to pH=3 by the addition of potassium hydrogen sulfate with ice bath cooling while layered over methylene chloride (100 mL). The layers were separated and the aqueous layer was extracted with methylene chloride (2×200 mL). The combined organic layers were washed with water (75 mL), dried over sodium sulfate, filtered and evaporated under reduced pressure to give an off white foam. The residue was chromatographed on a wet-packed silica gel column (6.5×28 cm) eluting with 3-4% methanol in methylene chloride. The appropriate fractions were combined and evaporated to give 4.4 g (70%) of [1-(5-oxo-4,5-dihydro-[1,2,4]oxadiazol-3-yl)-spiro[2.5]oct-1-ylmethyl]-carbamic acid tert-butyl ester as a white foam: 1H NMR (300 MHz, CDCl3) δ0.78 (d, J=5.3 Hz, 1H), 1.44 (s, 9H), 1.3-1.7 (m, 11H), 3.24 (dd, J=5.0, 13.9 Hz, 1H), 3.84 (dd, J=5.0, 13.9 Hz, 1H), 4.97 (s, 1H); MS (APCI) m/z 324 [M+H]+.

Workup

  1. additionwas added
  2. temperatureThe solution was heated
  3. temperatureto reflux for an additional 4 hours
  4. customthe solvent was removed under reduced pressure
  5. customThe residue was partitioned between ether (200 mL) and 1N NaOH (75 mL)
  6. extractionThe organic layer was extracted with 1N NaOH (2×75 mL)
  7. washThe combined aqueous layers were washed with ether (100 mL)
  8. additionThe aqueous layer was acidified to pH=3 by the addition of potassium hydrogen sulfate with ice bath
  9. temperaturecooling while layered over methylene chloride (100 mL)
  10. customThe layers were separated
  11. extractionthe aqueous layer was extracted with methylene chloride (2×200 mL)
  12. washThe combined organic layers were washed with water (75 mL)
  13. dry with materialdried over sodium sulfate
  14. filtrationfiltered
  15. customevaporated under reduced pressure
  16. customto give an off white foam
  17. customThe residue was chromatographed on a wet-packed silica gel column (6.5×28 cm)
  18. washeluting with 3-4% methanol in methylene chloride
  19. customevaporated

Sources & evidence

ORD record
ord-ce8b13fd0b8149d4940ff70d3f4687f3
Source dataset
uspto-grants-2007_07
Patent number
US07250433B2

Reaction notes

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