Water → HCID 69715450, compound

HRID 733232Notes

Reaction equation

HRID 733232 reaction equation
[H-].[Na+].[Cl: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.[Cl: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>C(OCC)(=O)C>[Cl: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.[Cl: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

8

Reactant 5

HCID 962WaterHCID 80711,2-DimethoxyethaneHCID 24758Sodium hydrideHCID 22025424HCID 22025424, compoundHCID 22025456HCID 22025456, compound

Product 2

HCID 69715450HCID 69715450, compoundHCID 86591363HCID 86591363, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
20 °C

Procedure

Ethyl (5-chloro-2-isobutyl-3-oxo-2,3-dihydro-1H-isoindol-1-yl)acetate and ethyl (6-chloro-2-isobutyl-3-oxo-2,3-dihydro-1H-isoindol-1-yl)acetate are prepared as described in Example 2, starting with 4 g of 60% sodium hydride in 200 cm3 of 1,2-dimethoxyethane, 20.3 cm3 of triethyl phosphonoacetate and 12 g of 5-chloro-3-hydroxy-2-isobutyl-2,3-dihydroisoindol-1-one and 6-chloro-3-hydroxy-2-isobutyl-2,3-dihydroisoindol-1-one. The mixture is refluxed for 18 hours and is then cooled to a temperature in the region of 20° C. The reaction mixture is treated with 200 cm3 of water and then with 100 cm3 of ethyl acetate. After separation of the phases by settling, the aqueous phase is extracted twice with 200 cm3 of ethyl acetate. The organic extracts are combined, washed with 100 cm3 of 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 (60 kPa) on a cartridge of silica gel (particle size 32-63 μm), eluting with successive mixtures of cyclohexane/ethyl acetate (90/10 and then 80/20 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. 3.1 g of ethyl (5-chloro-2-isobutyl-3-oxo-2,3-dihydro-1H-isoindol-1-yl)acetate and ethyl (6-chloro-2-isobutyl-3-oxo-2,3-dihydro-1H-isoindol-1-yl)acetate are thus obtained in the form of a viscous yellow oil. (Rf=0.34, thin layer chromatography on silica gel, eluent: cyclohexane/ethyl acetate (75/25 by volume)).

Workup

  1. temperatureThe mixture is refluxed for 18 hours
  2. customAfter separation of the phases
  3. extractionthe aqueous phase is extracted twice with 200 cm3 of ethyl acetate
  4. washwashed with 100 cm3 of brine
  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 40° C
  8. customThe residue is purified by chromatography under argon pressure (60 kPa) on a cartridge of silica gel (particle size 32-63 μm)
  9. washeluting with successive mixtures of cyclohexane/ethyl acetate (90/10
  10. concentrationconcentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C

Sources & evidence

ORD record
ord-905509a094244ca6a484f0fb5b4ed08d
Source dataset
uspto-grants-2009_09
Patent number
US07589117B2

Reaction notes

Loading…