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

HRID 733259Notes

Reaction equation

HRID 733259 reaction equation
[CH2:1]([N:5]1[C:9](=[O:10])[C:8]2=[C:11]([CH3:15])[CH:12]=[CH:13][CH:14]=[C:7]2[C:6]1=[O:16])[CH:2]([CH3:4])[CH3:3].O>CO.[BH4-].[K+]>[CH3:15][C:11]1[CH:12]=[CH:13][CH:14]=[C:7]2[C:8]=1[C:9](=[O:10])[N:5]([CH2:1][CH:2]([CH3:3])[CH3:4])[CH:6]2[OH:16].[CH3:15][C:11]1[CH:12]=[CH:13][CH:14]=[C:7]2[C:8]=1[CH:9]([OH:10])[N:5]([CH2:1][CH:2]([CH3:3])[CH3:4])[C:6]2=[O:16]

Participants

6

Reactant 2

HCID 962WaterHCID 22025457N-isobutyl-3-methylphthalimide

Product 2

HCID 220254364-Methyl-3-hydroxy-2-isobutyl-2,3-dihydroisoindol-1-oneHCID 220254597-Methyl-3-hydroxy-2-isobutyl-2,3-dihydroisoindol-1-one

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 4192641Potassium borohydrideSolvent

Conditions

Temperature
20 °C

Procedure

4-Methyl-3-hydroxy-2-isobutyl-2,3-dihydroisoindol-1-one and 7-methyl-3-hydroxy-2-isobutyl-2,3-dihydroisoindol-1-one are prepared as described in Example 1, starting with 5.4 g of N-isobutyl-3-methylphthalimide in 20 cm3 of methanol and 1.4 g of potassium borohydride. The reaction mixture is stirred at a temperature in the region of 20° C. for 65 hours and is then cooled to a temperature in the region of 0° C. and 10 cm3 of distilled water are added dropwise. The mixture is concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. and the residue is taken up successively in diethyl ether and then in dichloromethane. The precipitate obtained is filtered off and the filtrate is then concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. The residue is purified by chromatography under argon pressure (50 kPa) on a column of silica gel (particle size 15-40 μm), eluting with a mixture of cyclohexane/ethyl acetate (70/30 by volume). The fractions comprising each expected product are combined and concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. The fractions comprising a mixture of the two expected products are combined and concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. The residue is purified again by chromatography under argon pressure (50 kPa) on a column of silica gel (particle size 15-40 μm), eluting with a mixture of cyclohexane/ethyl acetate (80/20 by volume). The fractions comprising each expected product are combined and concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. 0.74 g of 7-methyl-3-hydroxy-2-isobutyl-2,3-dihydroisoindol-1-one in the form of a white powder (Rf=0.54, thin layer chromatography on silica gel, eluent: cyclohexane/ethyl acetate (50/50 by volume)) and 0.89 g of 4-methyl-3-hydroxy-2-isobutyl-2,3-dihydroisoindol-1-one in the form of a cottony white solid (Rf=0.40, thin layer chromatography on silica gel, eluent: cyclohexane/ethyl acetate (50/50 by volume)) are thus obtained.

Workup

  1. custom4-Methyl-3-hydroxy-2-isobutyl-2,3-dihydroisoindol-1-one and 7-methyl-3-hydroxy-2-isobutyl-2,3-dihydroisoindol-1-one are prepared
  2. additionare added dropwise
  3. concentrationThe mixture is concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C.
  4. customThe precipitate obtained
  5. filtrationis filtered off
  6. concentrationthe filtrate is then concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C
  7. customThe residue is purified by chromatography under argon pressure (50 kPa) on a column of silica gel (particle size 15-40 μm)
  8. washeluting with a mixture of cyclohexane/ethyl acetate (70/30 by volume)
  9. concentrationconcentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C
  10. additionThe fractions comprising a mixture of the two expected products
  11. concentrationconcentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C
  12. customThe residue is purified again by chromatography under argon pressure (50 kPa) on a column of silica gel (particle size 15-40 μm)
  13. washeluting with a mixture of cyclohexane/ethyl acetate (80/20 by volume)
  14. concentrationconcentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C

Sources & evidence

ORD record
ord-6bf732e96bd64f24aac0e8f630bbd3df
Source dataset
uspto-grants-2009_09
Patent number
US07589117B2

Reaction notes

Loading…