Water → Tert-butyl 3-(2-(2-(2-(1,3-dioxoisoindolin-2-yl)ethoxy)ethoxy)ethoxy)propanoate

HRID 870218Notes

Reaction equation

HRID 870218 reaction equation
S(O[CH2:12][CH2:13][O:14][CH2:15][CH2:16][O:17][CH2:18][CH2:19][O:20][CH2:21][CH2:22][C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])(C1C=CC(C)=CC=1)(=O)=O.[C:30]1(=[O:40])[NH:34][C:33](=[O:35])[C:32]2=[CH:36][CH:37]=[CH:38][CH:39]=[C:31]12.[K].O>CN(C=O)C>[O:35]=[C:33]1[C:32]2[C:31](=[CH:39][CH:38]=[CH:37][CH:36]=2)[C:30](=[O:40])[N:34]1[CH2:12][CH2:13][O:14][CH2:15][CH2:16][O:17][CH2:18][CH2:19][O:20][CH2:21][CH2:22][C:23]([O:25][C:26]([CH3:27])([CH3:29])[CH3:28])=[O:24]

Participants

5

Reactant 3

HCID 962WaterHCID 24194345Phthalimide potassium saltHCID 60146205Tos-PEG4-t-butyl ester

Product 1

HCID 67458913Tert-butyl 3-(2-(2-(2-(1,3-dioxoisoindolin-2-yl)ethoxy)ethoxy)ethoxy)propanoateYield 80%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

Into a 250-mL round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed a solution of tert-butyl 3-(2-(2-(2-(tosyloxy)ethoxy)ethoxy)ethoxy)propanoate (13.4 g, 30.98 mmol, 1.00 equiv) in anhydrous DMF (100 mL) followed by potassium phthalimide (7.5 g, 40.49 mmol, 1.31 equiv). The resulting solution was heated to 100° C. and stirred for 3 h. The reaction progress was monitored by LCMS. The DMF was removed under vacuum to afford a brown oil residue. To the residue was added 200 mL water and the mixture was extracted with 3×50 mL of ethyl acetate. The combined organic layers were washed with saturated brine and dried over anhydrous sodium sulfate. After evaporation of solvent, The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (0˜1:3). The solvent was removed from fractions containing phthalimide and the residue was washed with 20% ethyl acetate/petroleum ether to yield 10.1 g (78%) of tert-butyl 3-(2-(2-(2-(1,3-dioxoisoindolin-2-yl)ethoxy)ethoxy)ethoxy)propanoate as pale yellow oil.

Workup

  1. customInto a 250-mL round-bottom flask purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. customThe DMF was removed under vacuum
  4. customto afford a brown oil residue
  5. extractionthe mixture was extracted with 3×50 mL of ethyl acetate
  6. washThe combined organic layers were washed with saturated brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. customAfter evaporation of solvent
  9. customThe solvent was removed from fractions
  10. additioncontaining phthalimide
  11. washthe residue was washed with 20% ethyl acetate/petroleum ether

Sources & evidence

ORD record
ord-5b27fae5d22e4f178ac12dee16842627
Source dataset
uspto-grants-2015_03
Patent number
US08969377B2

Reaction notes

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