Water → 4,7-Difluoro-3-hydroxy-2-isobutyl-2,3-dihydroisoindol-1-one

HRID 733256Notes

Reaction equation

HRID 733256 reaction equation
[F:1][C:2]1[CH:16]=[CH:15][C:14]([F:17])=[C:4]2[C:5]([N:7]([CH2:10][CH:11]([CH3:13])[CH3:12])[C:8](=[O:9])[C:3]=12)=[O:6].O>CO.[BH4-].[K+]>[F:1][C:2]1[CH:16]=[CH:15][C:14]([F:17])=[C:4]2[C:3]=1[CH:8]([OH:9])[N:7]([CH2:10][CH:11]([CH3:12])[CH3:13])[C:5]2=[O:6]

Participants

5

Reactant 2

HCID 962WaterHCID 220254173,6-difluoro-N-isobutylphthalimide

Product 1

HCID 179664254,7-Difluoro-3-hydroxy-2-isobutyl-2,3-dihydroisoindol-1-oneYield 87.9%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 4192641Potassium borohydrideSolvent

Conditions

Temperature
20 °C

Procedure

4,7-Difluoro-3-hydroxy-2-isobutyl-2,3-dihydroisoindol-1-one is prepared as described in Example 1, starting with 6.41 g of 3,6-difluoro-N-isobutylphthalimide in 70 cm3 of methanol and 1.44 g of potassium borohydride. The reaction mixture is stirred at a temperature in the region of 20° C. for 3 hours and is then cooled to a temperature in the region of 0° C. and 45 cm3 of distilled water are added dropwise. The methanol is then partially evaporated off under reduced pressure (2 kPa) at a temperature in the region of 30° C., followed by addition of 80 cm3 of dichloromethane. After separation of the phases by settling, the aqueous phase is extracted twice 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 30° C. The residue is dried in a desiccator under reduced pressure (2 kPa) at a temperature in the region of 20° C. 5.68 g of 4,7-difluoro-3-hydroxy-2-isobutyl-2,3-dihydroisoindol-1-one are thus obtained in the form of a yellow solid melting at 129.5° C. (Rf=0.48, thin layer chromatography on silica gel, eluent: cyclohexane/ethyl acetate (50/50 by volume)).

Workup

  1. custom4,7-Difluoro-3-hydroxy-2-isobutyl-2,3-dihydroisoindol-1-one is prepared
  2. additionare added dropwise
  3. customThe methanol is then partially evaporated off under reduced pressure (2 kPa) at a temperature in the region of 30° C.
  4. additionfollowed by addition of 80 cm3 of dichloromethane
  5. customAfter separation of the phases
  6. extractionthe aqueous phase is extracted twice with 80 cm3 of dichloromethane
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 30° C
  10. customThe residue is dried in a desiccator under reduced pressure (2 kPa) at a temperature in the region of 20° C

Sources & evidence

ORD record
ord-e85c875821c04067a2f7a16a2277296b
Source dataset
uspto-grants-2009_09
Patent number
US07589117B2

Reaction notes

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