Water → (S)-1-[2-(Acetyloxy)-1-phenylethyl]-2,5-dihydro-1H-pyrrol-2,5-dione

HRID 1736059Notes

Reaction equation

HRID 1736059 reaction equation
C[Si](C)(C)NC(N[Si](C)(C)C)=O.[C:13]1([C@@H:19]([CH2:21][OH:22])[NH2:20])[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[C:23]1(=[O:29])[O:28][C:26](=O)[CH:25]=[CH:24]1.O.C1C[O:34][CH2:33][CH2:32]1>>[C:33]([O:22][CH2:21][C@@H:19]([N:20]1[C:23](=[O:29])[CH:24]=[CH:25][C:26]1=[O:28])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)(=[O:34])[CH3:32]

Participants

6

Reactant 5

HCID 962WaterHCID 7923Maleic AnhydrideHCID 8028TetrahydrofuranHCID 875621,3-Bis(trimethylsilyl)ureaHCID 1347972-Amino-2-phenylethan-1-ol

Product 1

HCID 9859949(S)-1-[2-(Acetyloxy)-1-phenylethyl]-2,5-dihydro-1H-pyrrol-2,5-dioneYield 83%

Procedure

1,3-Bis(trimethylsilyl)urea (0.745 g, 3.65 mM) was added to (S)-(+)-2-phenylglycinol (0.5 g, 3.65 mM) dissolved in THF (10 ml, distilled from Na/benzophenone). The mixture was refluxed for 1 hr. A precipitate formed. Maleic anhydride (0.376 g, 3.83 mM) was added and the mixture refluxed for 0.5 hr. H2O (66 μl, 3.65 mM) was added to the cooled mixture and stirred for 30 min. to form the intermediate ##STR55## which was not recovered from the reaction mixture. Tetrabutyl-ammonium fluoride (TBAF·3H2O, 0.115 g, 0.365 mM), acetic anhydride (AC2O) (3.44 ml, 36.5 mM), and triethylamine (TEA) (3.0 ml, 21.9 mM) were added and the mixture refluxed for 2.5 hrs. After cooling to room temperature, H2O (15 ml) was added and stirred for 1 hr. The reaction mixture was taken up in EtOAc (75 ml), washed with water (2×50 ml), 5% NaHCO3 (50 ml), brine (25 ml), dried (MgSO4), and evaporated to a black oil: 0.88 g. The oil was Kugalrohr distilled under vacuum (~0.3 mm), oven temperature 110°-30°, giving title compound as a colorless oil: 0.79 g (83% yield). TLC (silica gel, EtOAc/hexane 7:3 visualized with UV and KMnO4) showed the product as one spot at Rf 0.60.

Workup

  1. temperatureThe mixture was refluxed for 1 hr
  2. customA precipitate formed
  3. temperaturethe mixture refluxed for 0.5 hr
  4. customto form the intermediate ##STR55## which
  5. customwas not recovered from the reaction mixture
  6. additionTetrabutyl-ammonium fluoride (TBAF·3H2O, 0.115 g, 0.365 mM), acetic anhydride (AC2O) (3.44 ml, 36.5 mM), and triethylamine (TEA) (3.0 ml, 21.9 mM) were added
  7. temperaturethe mixture refluxed for 2.5 hrs
  8. additionH2O (15 ml) was added
  9. stirringstirred for 1 hr
  10. washwashed with water (2×50 ml), 5% NaHCO3 (50 ml), brine (25 ml)
  11. dry with materialdried (MgSO4)
  12. customevaporated to a black oil
  13. distillationdistilled under vacuum (~0.3 mm), oven temperature 110°-30°

Sources & evidence

ORD record
ord-e14c54ebf37547a68b2b1fa8bc719ec7
Source dataset
uspto-grants-1996_07
Patent number
US05539126

Reaction notes

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