Sulfuric Acid → (2S,4R)-4-methanesulfonyloxy-1(4-nitrobenzyloxycarbonyl)-2-(2-oxoimidazolidin-1-yl)carbonylpyrrolidine

HRID 1650838Notes

Reaction equation

HRID 1650838 reaction equation
P(Cl)(Cl)(Cl)=O.[CH3:6][S:7]([O:10][C@H:11]1[CH2:15][N:14]([C:16]([O:18][CH2:19][C:20]2[CH:25]=[CH:24][C:23]([N+:26]([O-:28])=[O:27])=[CH:22][CH:21]=2)=[O:17])[C@H:13]([C:29]([OH:31])=O)[CH2:12]1)(=[O:9])=[O:8].[CH2:32]1[NH:37][C:35](=[O:36])[NH:34][CH2:33]1.S(=O)(=O)(O)O>O1CCCC1.O.C(OCC)(=O)C.CN(C)C=O>[CH3:6][S:7]([O:10][C@H:11]1[CH2:15][N:14]([C:16]([O:18][CH2:19][C:20]2[CH:25]=[CH:24][C:23]([N+:26]([O-:28])=[O:27])=[CH:22][CH:21]=2)=[O:17])[C@H:13]([C:29]([N:34]2[CH2:33][CH2:32][NH:37][C:35]2=[O:36])=[O:31])[CH2:12]1)(=[O:8])=[O:9]

Participants

9

Reactant 4

HCID 1118Sulfuric AcidHCID 84532-ImidazolidinoneHCID 24813Phosphorus oxychlorideHCID 13502650trans-4-methanesulfonyloxy-1-(4-nitrobenzyloxycarbonyl)-L-proline

Product 1

HCID 15056143(2S,4R)-4-methanesulfonyloxy-1(4-nitrobenzyloxycarbonyl)-2-(2-oxoimidazolidin-1-yl)carbonylpyrrolidineYield 84.2%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
5 °C

Procedure

To a mixture of N,N-dimethylformamide (0.6 ml) and tetrahydrofuran (1.2 ml) was added dropwise phosphorus oxychloride (0.58 ml) at -5° C. and the mixture was stirred at 5° C. for 5 minutes. To the mixture was added a solution of (2S,4R)-4-methanesulfonyloxy-1-(4-nitrobenzyloxycarbonyl)proline (2.0 g) in tetrahydrofuran (20 ml) under ice-cooling. The solution was stirred at the same temperature for 30 minutes. To a solution were added ethylene urea (2.22 g) and concentrated sulfuric acid (0.035 ml), and the mixture was stirred at 45°-50° C. for 3 hours. Ethyl acetate (100 ml) and water (40 ml) was poured into the reaction mixture. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and evaporated in vacuo to give a residue. The residue was chromatographed on silica gel (100 g) eluting with a mixture of chloroform and methanol (9:1, V/V). The fractions containing the desired compound were collected and evaporated in vacuo to give (2S,4R)-4-methanesulfonyloxy-1-(4-nitrobenzyloxycarbonyl)-2-(2-oxoimidazolidin-1-yl)carbonylpyrrolidine (1.98 g).

Workup

  1. temperaturecooling
  2. stirringThe solution was stirred at the same temperature for 30 minutes
  3. stirringthe mixture was stirred at 45°-50° C. for 3 hours
  4. washThe organic layer was washed with saturated aqueous sodium chloride
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customevaporated in vacuo
  7. customto give a residue
  8. customThe residue was chromatographed on silica gel (100 g)
  9. washeluting with a mixture of chloroform and methanol (9:1, V/V)
  10. additionThe fractions containing the desired compound
  11. customwere collected
  12. customevaporated in vacuo

Sources & evidence

ORD record
ord-5d7910c57b4d493f81a3cea44747f497
Source dataset
uspto-grants-1990_05
Patent number
US04925838

Reaction notes

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