Hydroxylamine → 1-Hydroxy-(3R,4R)-2,5-Dioxo-3,4-dibenzoyloxypyrrolidine

HRID 1726940Notes

Reaction equation

HRID 1726940 reaction equation
[O:1]=[C:2]1[C@H:6]([O:7][C:8](=[O:15])[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[C@@H:5]([O:16][C:17](=[O:24])[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:4](=O)[O:3]1.C(#N)C.[NH2:29][OH:30].O>C1(C)C=CC=CC=1>[OH:30][N:29]1[C:2](=[O:1])[C@H:6]([O:7][C:8](=[O:15])[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[C@@H:5]([O:16][C:17](=[O:24])[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:4]1=[O:3]

Participants

6

Reactant 4

HCID 787HydroxylamineHCID 962WaterHCID 6342AcetonitrileHCID 2733743(3R,4R)-3,4-Bis(benzoyloxy)dihydro-2,5-furandione

Product 1

HCID 111319931-Hydroxy-(3R,4R)-2,5-Dioxo-3,4-dibenzoyloxypyrrolidineYield 87.1%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
4 °C

Procedure

To a 3-neck 5 L round bottom flask fitted with a mechanical stirrer and a Teflon coated temperature probe was added (29) (2.79 mol) followed by acetonitrile (2 L). The suspension was cooled in an ice bath to 4° C., followed by the addition of 50% aqueous hydroxylamine (180 mL, 2.93 mol) over 1 h. The starting material gradually dissolved during the addition and the reaction mixture was warmed to 20° C. and stirred for 1 h. The reaction mixture was concentrated in vacuo, diluted with EtOAc (1 L) and washed with 1 N HCl (2×1 L). The organic phase was separated and concentrated in vacuo to afford a viscous red syrup. The syrup was then heated for two hours in toluene (2.5 L) at 100° C. with azeotropic removal of water. The syrup gradually dissolved and then the product crystallized. After cooling to room temperature the solid was collected by filtration, washed with 10% acetone in hexane (2×1L) and dried in a vacuum oven to afford the title compound (30) (862 g, 2.43 mol, 87% yield) as a white solid. 1H NMR (CDCl3, 400 MHz): δ 5.85 (s, 2H), 7.45 (app. t, 4H), 7.65 (app t, 2H), 8.05 (m, 4H).

Workup

  1. customTo a 3-neck 5 L round bottom flask fitted with a mechanical stirrer
  2. dissolutionThe starting material gradually dissolved during the addition
  3. temperaturethe reaction mixture was warmed to 20° C.
  4. concentrationThe reaction mixture was concentrated in vacuo
  5. additiondiluted with EtOAc (1 L)
  6. washwashed with 1 N HCl (2×1 L)
  7. customThe organic phase was separated
  8. concentrationconcentrated in vacuo
  9. customto afford a viscous red syrup
  10. dissolutionThe syrup gradually dissolved
  11. customthe product crystallized
  12. temperatureAfter cooling to room temperature the solid
  13. filtrationwas collected by filtration
  14. washwashed with 10% acetone in hexane (2×1L)
  15. customdried in a vacuum oven

Sources & evidence

ORD record
ord-90d999cc94424b0ab57049a5169429e8
Source dataset
uspto-grants-2009_02
Patent number
US07494985B2

Reaction notes

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