Potassium Carbonate → (7aS,6S)-2-(3,5-dichloro-phenyl)-6-hydroxy-tetrahydro-pyrrolo[1,2-c]imidazole-1,3-dione

HRID 49965

Reaction equation

HRID 49965 reaction equation
CO[C:3](=[O:10])[C@@H:4]1[CH2:8][C@H:7]([OH:9])[CH2:6][NH:5]1.C([O-])([O-])=O.[K+].[K+].[Cl:17][C:18]1[CH:19]=[C:20]([N:25]=[C:26]=[O:27])[CH:21]=[C:22]([Cl:24])[CH:23]=1>CN(C=O)C>[Cl:17][C:18]1[CH:19]=[C:20]([N:25]2[C:3](=[O:10])[C@@H:4]3[CH2:8][C@H:7]([OH:9])[CH2:6][N:5]3[C:26]2=[O:27])[CH:21]=[C:22]([Cl:24])[CH:23]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 944603,5-Dichlorophenyl isocyanateHCID 7021050methyl (2S,4S)-4-hydroxypyrrolidine-2-carboxylate

Product 1

HCID 12096649(7aS,6S)-2-(3,5-dichloro-phenyl)-6-hydroxy-tetrahydro-pyrrolo[1,2-c]imidazole-1,3-dioneYield 23.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of cis-4-hydroxy-L-proline methyl ester (0.53 g) (0.0036 mol) in 10 mL of DMF cooled at 0° C. was added K2CO3 (0.52 g) (1.1 eq.), then 3,5-dichlorophenyl isocyanate (0.75 g) (1.1 eq.). The reaction was stirred overnight at RT and the insoluble material removed by filtration. The solution was concentrated under vacuum and the residue dissolved in DCM. The organic layer was washed with water, dried over MgSO4, and evaporated under reduced pressure. The resulting residue was purified on a SiO2 column (eluent: DCM/acetone-95/5) to afford the titled compound as a white solid (0.25 g). NMR (CDCl3, 200 MHz): 7.35 (3H, s), 4.45 (1H, m), 4.30 (1H, dd), 4.0 (1H, d), 3.1 (1H, dd), 2.35-2.2 (2H, m), 1.95 (1H, bs, OH).

Workup

  1. customthe insoluble material removed by filtration
  2. concentrationThe solution was concentrated under vacuum
  3. dissolutionthe residue dissolved in DCM
  4. washThe organic layer was washed with water
  5. dry with materialdried over MgSO4
  6. customevaporated under reduced pressure
  7. customThe resulting residue was purified on a SiO2 column (eluent: DCM/acetone-95/5)

Sources & evidence

ORD record
ord-4c8d7628b5954f35b54cdaa39e5ad743
Source dataset
uspto-grants-2004_03
Patent number
US06710064B2

Linked notes

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