p-Toluenesulfonic acid → 3,6-difluoro-N-isobutylphthalimide

HRID 1792947Notes

Reaction equation

HRID 1792947 reaction equation
[F:1][C:2]1[CH:12]=[CH:11][C:10]([F:13])=[C:4]2[C:5]([O:7][C:8](=[O:9])[C:3]=12)=O.[CH2:14]([NH2:18])[CH:15]([CH3:17])[CH3:16].C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[F:13][C:10]1[CH:11]=[CH:12][C:2]([F:1])=[C:3]2[C:8]([N:18]([CH2:14][CH:15]([CH3:17])[CH3:16])[C:5](=[O:7])[C:4]=12)=[O:9]

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 6558IsobutylamineHCID 5139183,6-Difluorophthalic anhydride

Product 1

HCID 220254173,6-difluoro-N-isobutylphthalimide

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
20 °C

Procedure

3,6-Difluoro-N-isobutylphthalimide is prepared as described in Example 2, starting with 5.0 g of 3,6-difluorophthalic anhydride, 2.7 cm3 of isobutylamine and a catalytic amount of para-toluenesulfonic acid in 50 cm3 of toluene. The reaction mixture is refluxed for 3 hours. After cooling to a temperature in the region of 20° C., the reaction mixture is filtered and then concentrated to dryness under reduced pressure (2 kPa). The residue is taken up in 50 cm3 of saturated aqueous sodium bicarbonate solution and washed 3 times with 80 cm3 of dichloromethane. The organic extracts are combined, dried over magnesium sulfate, filtered and then concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. 6.41 g of 3,6-difluoro-N-isobutylphthalimide are thus obtained in the form of a pale yellow solid. (Rf=0.74, thin layer chromatography on silica gel, eluent: cyclohexane/ethyl acetate (50/50 by volume)).

Workup

  1. custom3,6-Difluoro-N-isobutylphthalimide is prepared
  2. temperatureThe reaction mixture is refluxed for 3 hours
  3. filtrationthe reaction mixture is filtered
  4. concentrationconcentrated to dryness under reduced pressure (2 kPa)
  5. washwashed 3 times with 80 cm3 of dichloromethane
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C

Sources & evidence

ORD record
ord-f52fc0d1191e4205b49c3b05602ca96c
Source dataset
uspto-grants-2006_07
Patent number
US07078428B2

Reaction notes

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