Water → 1-Benzyl-4-[3-(tert-butoxycarbonylamino)-1-oxocyclobutan-3-yl]-2-pyrrolidone

HRID 1279653Notes

Reaction equation

HRID 1279653 reaction equation
[CH2:1]([N:8]1[CH2:12][CH:11]([C:13]2([NH:18][C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:16][CH:15]([OH:17])[CH2:14]2)[CH2:10][C:9]1=[O:26])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.O.C(OCC)(=O)C>CS(C)=O>[CH2:1]([N:8]1[CH2:12][CH:11]([C:13]2([NH:18][C:19]([O:21][C:22]([CH3:24])([CH3:23])[CH3:25])=[O:20])[CH2:16][C:15](=[O:17])[CH2:14]2)[CH2:10][C:9]1=[O:26])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 184278241-Benzyl-4-[3-(tert-butoxycarbonylamino)-1-hydroxycyclobutan-3-yl]-2-pyrrolidone

Product 1

HCID 184278081-Benzyl-4-[3-(tert-butoxycarbonylamino)-1-oxocyclobutan-3-yl]-2-pyrrolidoneYield 96.3%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

A 4.89 g (13.6 mmol) portion of 1-benzyl-4-[3-(tert-butoxycarbonylamino)-1-hydroxycyclobutan-3-yl]-2-pyrrolidone was dissolved in 100 ml of dimethyl sulfoxide to which, while cooling in an ice bath with stirring, were then added 6.24 ml (44.8 mmol) of triethylamine and 6.47 g (10.7 mmol) of sulfur trioxide-pyridine complex in that order, subsequently carrying out 14 hours of stirring at room temperature. While cooling in an ice bath with stirring, the reaction solution was mixed with water and then with ethyl acetate to effect separation of layers. The organic layer was washed with saturated brine, the aqueous layer was extracted with ethyl acetate and then the organic layers were combined and dried over anhydrous sodium sulfate. After filtration, the solvent was evaporated and the resulting residue was purified by a silica gel column chromatography to give 4.69 g (96.3%) of the title compound. Thereafter, optical resolution of Isomers F1 and F2 as enantiomers originated from the pyrrolidine 4 position asymmetric carbon atom of the thus obtained compound was carried out by HPLC under the following conditions.

Workup

  1. temperaturewhile cooling in an ice bath
  2. stirringof stirring at room temperature
  3. temperatureWhile cooling in an ice bath
  4. stirringwith stirring
  5. customseparation of layers
  6. washThe organic layer was washed with saturated brine
  7. extractionthe aqueous layer was extracted with ethyl acetate
  8. dry with materialdried over anhydrous sodium sulfate
  9. filtrationAfter filtration
  10. customthe solvent was evaporated
  11. customthe resulting residue was purified by a silica gel column chromatography

Sources & evidence

ORD record
ord-fb8625bb0aa1458296a0369d32d44fd0
Source dataset
uspto-grants-2002_09
Patent number
US06448266B1

Reaction notes

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