Water → HCID 69714493, compound

HRID 733236Notes

Reaction equation

HRID 733236 reaction equation
[H-].[Na+].[Br:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[C:9](=[O:13])[N:8]([CH2:14][CH:15]([CH3:17])[CH3:16])[CH:7]2O.[Br:19][C:20]1[CH:28]=[C:27]2[C:23]([CH:24](O)[N:25]([CH2:30][CH:31]([CH3:33])[CH3:32])[C:26]2=[O:29])=[CH:22][CH:21]=1.O.C[O:37][CH2:38][CH2:39]OC>>[Br:3][C:4]1[CH:5]=[C:6]2[C:10]([C:9](=[O:13])[N:8]([CH2:14][CH:15]([CH3:17])[CH3:16])[CH:7]2[CH2:39][C:38]([O:29][CH2:26][CH3:27])=[O:37])=[CH:11][CH:12]=1.[Br:19][C:20]1[CH:28]=[C:27]2[C:23](=[CH:22][CH:21]=1)[CH:24]([CH2:39][C:38]([O:13][CH2:9][CH3:10])=[O:37])[N:25]([CH2:30][CH:31]([CH3:33])[CH3:32])[C:26]2=[O:29]

Participants

7

Reactant 5

HCID 962WaterHCID 80711,2-DimethoxyethaneHCID 24758Sodium hydrideHCID 22025435HCID 22025435, compoundHCID 22025486HCID 22025486, compound

Product 2

HCID 69714493HCID 69714493, compoundHCID 86591364HCID 86591364, compound

Conditions

Temperature
20 °C

Procedure

Ethyl (5-bromo-2-isobutyl-3-oxo-2,3-dihydro-1H-isoindol-1-yl)acetate and ethyl (6-bromo-2-isobutyl-3-oxo-2,3-dihydro-1H-isoindol-1-yl)acetate are prepared as described in Example 2, starting with 5.0 g of 60% sodium hydride in 250 cm3 of 1,2-dimethoxyethane, 24.8 cm3 of triethyl phosphonoacetate and 23.7 g of 5-bromo-3-hydroxy-2-isobutyl-2,3-dihydroisoindol-1-one and 6-bromo-3-hydroxy-2-isobutyl-2,3-dihydroisoindol-1-one. The mixture is refluxed for 4 hours and then cooled to a temperature in the region of 20° C. The reaction mixture is treated with 300 cm3 of water and the mixture is then extracted with 3 times 250 cm3 of diethyl ether. The organic extracts are combined, washed with 300 cm3 of saturated brine, dried over magnesium sulfate, filtered and 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 (80 kPa), on a column of silica gel (particle size 32-63 μm), eluting with successive mixtures of cyclohexane/ethyl acetate (95/5 by volume), cyclohexane/methanol (90/10) and cyclohexane/ethyl acetate (80/20). 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. 3.72 g of ethyl (5-bromo-2-isobutyl-3-oxo-2,3-dihydro-1H-isoindol-1-yl)acetate and ethyl (6-bromo-2-isobutyl-3-oxo-2,3-dihydro-1H-isoindol-1-yl)acetate are thus obtained in the form of a colorless oil. (Rf=0.70, thin layer chromatography on silica gel, eluent: cyclohexane/ethyl acetate (50/50 by volume)).

Workup

  1. temperatureThe mixture is refluxed for 4 hours
  2. extractionthe mixture is then extracted with 3 times 250 cm3 of diethyl ether
  3. washwashed with 300 cm3 of saturated brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated 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 (80 kPa)
  8. washon a column of silica gel (particle size 32-63 μm), eluting with successive mixtures of cyclohexane/ethyl acetate (95/5 by volume), cyclohexane/methanol (90/10) and cyclohexane/ethyl acetate (80/20)
  9. concentrationconcentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C

Sources & evidence

ORD record
ord-d42357092248462d8cc1c4ac7d782c39
Source dataset
uspto-grants-2009_09
Patent number
US07589117B2

Reaction notes

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