1,1'-Carbonyldiimidazole → Imidazolin-2-one, 8

HRID 751109Notes

Reaction equation

HRID 751109 reaction equation
C([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@@H:10]([O:13][Si](C(C)(C)C)(C)C)[C@H:9]1[CH2:21][NH:22][C:23]1[CH:28]=[CH:27][C:26]([C:29]#[N:30])=[C:25]([Cl:31])[C:24]=1[CH3:32])=O)(C)(C)C.C(N1C=CN=C1)(N1C=CN=C1)=O.C1CCN2C(=NCCC2)CC1>C1COCC1.CCOC(C)=O.O>[Cl:31][C:25]1[C:24]([CH3:32])=[C:23]([N:22]2[CH2:21][C@@H:9]3[C@H:10]([OH:13])[CH2:11][CH2:12][N:8]3[C:6]2=[O:5])[CH:28]=[CH:27][C:26]=1[C:29]#[N:30]

Participants

7

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 59424841(2R,3R)-N-tert-Butyloxycarbonyl-3-(tert-butyldimethylsiloxy)-2-[(3-chloro-4-cyano-2-methylphenylamino)methyl]pyrrolidine

Product 1

HCID 16733585Imidazolin-2-one, 8Yield 5.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (2R,3R)-3-(tert-Butyldimethylsilanyloxy)-2-[(3-chloro-4-cyano-2-methylphenylamino)methyl]pyrrolidine-1-carboxylic acid tert-butyl ester (51E) (22 mg, 0.06 mmol) dissolved in THF (1 mL) was added 1,1′-carbonyldiimidazole (9.40 mg, 0.06 mmol) and the mixture was stirred at rt for 3 days, and then brought to reflux for 1 h. An aliquot (˜half of the reaction mixture) was treated with DBU (10 μL, 0.07 mmol) and the reaction mixture was heated at reflux overnight. The reaction was then diluted with EtOAc and water, and the layers were separated. The organic layer was washed with brine, concentrated under reduced pressure, and purified via preparative HPLC (Luna C-18, 21.2×100 mm, eluting with 60-100% solvent B (A=90% H2O—10% MeOH—0.1% TFA and B=10% H2O—90% MeOH—0.1% TFA) over 12 min; Flow rate at 20 mL/min. UV detection at 220 nm). The major peak was collected, concentrated and treated with TFA (2 mL) overnight. The reaction was concentrated and purified via preparative HPLC (Luna C-18, 21.2×100 mm, eluting with 40-100% solvent B (A=90% H2O—10% MeOH—0.1% TFA and B=10% H2O—90% MeOH—0.1% TFA) over 10 min; Flow rate at 20 mL/min. UV detection at 220 nm) to provide the title compound (1 mg). LC/MS m/z 292 [M+H]+.

Workup

  1. temperatureto reflux for 1 h
  2. temperaturethe reaction mixture was heated
  3. temperatureat reflux overnight
  4. customthe layers were separated
  5. washThe organic layer was washed with brine
  6. concentrationconcentrated under reduced pressure
  7. custompurified via preparative HPLC (Luna C-18, 21.2×100 mm
  8. washeluting with 60-100% solvent B (A=90% H2O—10% MeOH—0.1% TFA and B=10% H2O—90% MeOH—0.1% TFA) over 12 min
  9. customThe major peak was collected
  10. concentrationconcentrated
  11. additiontreated with TFA (2 mL) overnight
  12. concentrationThe reaction was concentrated
  13. custompurified via preparative HPLC (Luna C-18, 21.2×100 mm
  14. washeluting with 40-100% solvent B (A=90% H2O—10% MeOH—0.1% TFA and B=10% H2O—90% MeOH—0.1% TFA) over 10 min

Sources & evidence

ORD record
ord-631e9c10d8f4430b87b72582762a6c44
Source dataset
uspto-grants-2008_07
Patent number
US07405234B2

Reaction notes

Loading…