Water → 3-Hydroxy-2-(2-methylpropyl)-2,3-dihydro-1H-isoindol-1-one

HRID 733209Notes

Reaction equation

HRID 733209 reaction equation
[CH2:1]([N:5]1[C:9](=[O:10])[C:8]2=[CH:11][CH:12]=[CH:13][CH:14]=[C:7]2[C:6]1=[O:15])[CH:2]([CH3:4])[CH3:3].O>CO.[BH4-].[K+]>[OH:10][CH:9]1[C:8]2[C:7](=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:6](=[O:15])[N:5]1[CH2:1][CH:2]([CH3:4])[CH3:3]

Participants

5

Reactant 2

HCID 962WaterHCID 963802-(2-Methylpropyl)-1H-isoindole-1,3(2H)-dione

Product 1

HCID 148953493-Hydroxy-2-(2-methylpropyl)-2,3-dihydro-1H-isoindol-1-oneYield 88.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 4192641Potassium borohydrideSolvent

Conditions

Temperature
20 °C

Procedure

3-Hydroxy-2-isobutyl-2,3-dihydroisoindol-1-one is prepared as described in Example 1, starting with 6.5 g of N-isobutylphthalimide in 60 cm3 of methanol and 1.7 g of potassium borohydride. The reaction mixture is stirred at a temperature in the region of 20° C. for 20 hours and is then cooled to a temperature in the region of 0° C., followed by dropwise addition of 50 cm3 of distilled water. The methanol is then partially evaporated off under reduced pressure (2 kPa) at a temperature in the region of 35° C., and the residue is extracted three times with 60 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 25° C. to give a pale yellow oil, which is purified by chromatography under argon pressure (60 kPa) on a column of silica gel (particle size 40-63 μm), eluting with a cyclohexane/ethyl acetate mixture (60/40 by volume). The fractions comprising the expected product are combined and concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. 5.8 g of 3-hydroxy-2-isobutyl-2,3-dihydroisoindol-1-one are thus obtained in the form of a white solid melting at 82° C.

Workup

  1. custom3-Hydroxy-2-isobutyl-2,3-dihydroisoindol-1-one is prepared
  2. temperatureis then cooled to a temperature in the region of 0° C.
  3. customThe methanol is then partially evaporated off under reduced pressure (2 kPa) at a temperature in the region of 35° C.
  4. extractionthe residue is extracted three times with 60 cm3 of dichloromethane
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 25° C.
  8. customto give a pale yellow oil, which
  9. customis purified by chromatography under argon pressure (60 kPa) on a column of silica gel (particle size 40-63 μm)
  10. washeluting with a cyclohexane/ethyl acetate mixture (60/40 by volume)
  11. concentrationconcentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C

Sources & evidence

ORD record
ord-bb64bd5537d64242a139e7a42895875b
Source dataset
uspto-grants-2009_09
Patent number
US07589117B2

Reaction notes

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