Ammonium Chloride → 2-(1,3-Isoindolinedion-2-yl)-5-(2,2-dimethyl-3-methoxycarbonyl-propionyl)indane

HRID 1598561Notes

Reaction equation

HRID 1598561 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Li+].C([Li])CCC.[C:16]1(=[O:40])[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[C:18](=[O:25])[N:17]1[CH:26]1[CH2:34][C:33]2[C:28](=[CH:29][CH:30]=[C:31]([C:35](=[O:39])[CH:36]([CH3:38])[CH3:37])[CH:32]=2)[CH2:27]1.Br[CH2:42][C:43]([O:45][CH3:46])=[O:44].[Cl-].[NH4+]>O1CCCC1>[C:16]1(=[O:40])[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[C:18](=[O:25])[N:17]1[CH:26]1[CH2:34][C:33]2[C:28](=[CH:29][CH:30]=[C:31]([C:35](=[O:39])[C:36]([CH3:37])([CH3:38])[CH2:42][C:43]([O:45][CH3:46])=[O:44])[CH:32]=2)[CH2:27]1

Participants

7

Reactant 5

HCID 25517Ammonium ChlorideHCID 60984Methyl bromoacetateHCID 2733832Lithium HexamethyldisilazideHCID 189297332-(1,3-Isoindolinedion-2-yl)-5-(2-methylpropionyl)indaneHCID 178418339Butyllithium

Product 1

HCID 189297382-(1,3-Isoindolinedion-2-yl)-5-(2,2-dimethyl-3-methoxycarbonyl-propionyl)indaneYield 51.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-40 °C

Procedure

Lithium bis(trimethylsilyl)amide prepared from 1.78 g of 1,1,1,3,3,3-hexamethylsilazane and n-butyl lithium (6.9 ml of 1.6M hexane solution), dissolved in 50 ml of tetrahydrofuran was cooled to -40° C., and 3.30 g of 2-(1,3-isoindolinedion-2-yl)-5-(2-methylpropionyl)indane dissolved in 50 ml of tetrahydrofuran was added dropwise thereto over 15 minutes. The mixture was stirred at 0° C. for 20 minutes and cooled to -30° C. To the mixture was added dropwise 1.68 g of methyl bromoacetate dissolved in 10 ml of tetrahydrofuran, and the mixture was stirred at room temperature for 2.5 hours. To the reaction mixture was added a saturated ammonium chloride solution, the mixture was extracted with ethyl acetate, the extract was dried, and then the solvent was removed. The residue was purified by silica gel column chromatography (eluted by n-hexane:ethyl acetate =4:1). The resulting crystals were recrystallized from ethyl acetate-n-hexane to obtain 2.06 g of 2-(1,3-isoindolinedion-2-yl)-5-(2,2-dimethyl-3-methoxycarbonyl-propionyl)indane.

Workup

  1. additionwas added dropwise
  2. temperaturecooled to -30° C
  3. stirringthe mixture was stirred at room temperature for 2.5 hours
  4. extractionthe mixture was extracted with ethyl acetate
  5. customthe extract was dried
  6. customthe solvent was removed
  7. customThe residue was purified by silica gel column chromatography (eluted by n-hexane:ethyl acetate =4:1)
  8. customThe resulting crystals were recrystallized from ethyl acetate-n-hexane

Sources & evidence

ORD record
ord-ddde2845c71f418cb8bc8fc2ed367554
Source dataset
uspto-grants-1998_04
Patent number
US05739132

Reaction notes

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