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

HRID 1279665Notes

Reaction equation

HRID 1279665 reaction equation
[CH2:1]([N:8]1[CH2:12][CH:11]([C:13]2([C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH2:16][CH:15](O)[CH2:14]2)[CH2:10][C:9]1=[O:23])[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:37])CC)C.C(=O)(O)[O-].[Na+]>C(Cl)(Cl)Cl.ClCCl>[CH2:1]([N:8]1[CH2:12][CH:11]([C:13]2([C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH2:16][CH:15]([F:37])[CH2:14]2)[CH2:10][C:9]1=[O:23])[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 184277971-Benzyl-4-[3-(ethoxycarbonyl)-1-hydroxycyclobutan-3-yl]-2-pyrrolidone

Product 1

HCID 184278031-Benzyl-4-[3-(ethoxycarbonyl)-1-fluorocyclobutan-3-yl]-2-pyrrolidoneYield 80%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent

Procedure

A 495 mg (1.56 mmol) portion of 1-benzyl-4-[3-(ethoxycarbonyl)-1-hydroxycyclobutan-3-yl]-2-pyrrolidone (Isomer A) was dissolved in a mixed solvent consisting of 12 ml of toluene and 6 ml of dichloromethane to which, while cooling in an ice bath with stirring, was then added 839 μl (6.24 mmol) of diethylaminosulfur trifluoride, subsequently carrying out 20 hours of stirring at 40° 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 (n-hexane:ethyl acetate=2:1) to give 400 mg (80.0%) of the title compound.

Workup

  1. temperaturewhile cooling in an ice bath
  2. stirringof stirring at 40° 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 (n-hexane:ethyl acetate=2:1)

Sources & evidence

ORD record
ord-665a847fd75545f88914db7b2057520f
Source dataset
uspto-grants-2002_09
Patent number
US06448266B1

Reaction notes

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