Toluene → 1-Benzyl-4-[3-(tert-butoxycarbonylamino)-1-fluorocyclobutan-3-yl]-2-pyrrolidone

HRID 1279652Notes

Reaction equation

HRID 1279652 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](O)[CH2:14]2)[CH2:10][C:9]1=[O:26])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1(C)C=CC=CC=1.C(N(S(F)(F)[F:40])CC)C.C(=O)(O)[O-].[Na+]>C(Cl)(Cl)Cl.ClCCl>[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]([F:40])[CH2:14]2)[CH2:10][C:9]1=[O:26])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 1140TolueneHCID 123472(Diethylamino)sulfur trifluorideHCID 516892Sodium BicarbonateHCID 184278241-Benzyl-4-[3-(tert-butoxycarbonylamino)-1-hydroxycyclobutan-3-yl]-2-pyrrolidone

Product 1

HCID 184278001-Benzyl-4-[3-(tert-butoxycarbonylamino)-1-fluorocyclobutan-3-yl]-2-pyrrolidoneYield 53.6%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent

Procedure

A 1.79 g (4.96 mmol) portion of 1-benzyl-4-[3-(tert-butoxycarbonylamino)-1-hydroxycyclobutan-3-yl]-2-pyrrolidone (Isomer B2) was dissolved in a mixed solvent consisting of 50 ml of toluene and 20 ml of dichloromethane to which, while cooling in an ice bath with stirring, was then added 1.31 ml (9.92 mmol) of diethylaminosulfur trifluoride, subsequently carrying out 12 hours of stirring at 50° C. While cooling in an ice bath with stirring, the reaction solution was alkalified by slowly adding saturated sodium bicarbonate aqueous solution and then mixed with chloroform to carry out separation of layers, and the resulting organic layer was washed with saturated brine. The aqueous layer was again extracted with chloroform, and the organic layers were combined and dried over anhydrous sodium sulfate. After filtration, the solvent was evaporated under a reduced pressure and the resulting residue was purified by a silica gel column chromatography to give 964 mg (53.6%) of the title compound. 1H-NMR data of the thus obtained compound coincided with the aforementioned data of its enantiomer Isomer B1.

Workup

  1. temperaturewhile cooling in an ice bath
  2. stirringof stirring at 50° C
  3. temperatureWhile cooling in an ice bath
  4. stirringwith stirring
  5. customseparation of layers
  6. washthe resulting organic layer was washed with saturated brine
  7. extractionThe aqueous layer was again extracted with chloroform
  8. dry with materialdried over anhydrous sodium sulfate
  9. filtrationAfter filtration
  10. customthe solvent was evaporated under a reduced pressure
  11. customthe resulting residue was purified by a silica gel column chromatography

Sources & evidence

ORD record
ord-d452baa4f1264b6faf2dde13255647a7
Source dataset
uspto-grants-2002_09
Patent number
US06448266B1

Reaction notes

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