Water → Tert-butyl 2-(1,3-bis(1,3-dioxoisoindolin-2-yl)propan-2-yloxy)ethylcarbamate

HRID 1476929Notes

Reaction equation

HRID 1476929 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][O:11][CH:12]([CH2:19]CS([O-])(=O)=O)[CH2:13]CS([O-])(=O)=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:25]1(=[O:35])[NH:29][C:28](=[O:30])[C:27]2=[CH:31][CH:32]=[CH:33][CH:34]=[C:26]12.[K].[OH2:37]>CN(C)C=O>[O:30]=[C:28]1[C:27]2[C:26](=[CH:34][CH:33]=[CH:32][CH:31]=2)[C:25](=[O:35])[N:29]1[CH2:19][CH:12]([O:11][CH2:10][CH2:9][NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[CH2:13][N:29]1[C:25](=[O:37])[C:26]2[C:27](=[CH:31][CH:32]=[CH:33][CH:34]=2)[C:28]1=[O:30]

Participants

5

Reactant 3

HCID 962WaterHCID 24194345Phthalimide potassium saltHCID 131736472HCID 131736472, compound

Product 1

HCID 67976238Tert-butyl 2-(1,3-bis(1,3-dioxoisoindolin-2-yl)propan-2-yloxy)ethylcarbamateYield 78.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A 20 L 4-neck round-bottom flask was flushed with N2. Then charged a solution of 2-(2-(tert-butoxycarbonylamino)ethoxy)propane-1,3-diyl-dimethanesulfonate (929 g, 2.37 mol, 1.0 eq) in N,N-dimethylformamide (9300 mL) and potassium phthalimide (2194 g, 11.85 mol, 5.0 eq). The resulting mixture was stirred for 18 hours at 70˜75° C. in an oil bath. The reaction progress was monitored with LCMS. The reaction mixture was cooled to 20˜30° C., then added icy water (28 L) with stirring. The mixture was stirred for 30 minutes, and then filtered. The filter cake was dried under vacuum at 60° C. to give 919 g (78.5%) tert-butyl 2-(1,3-bis(1,3-dioxoisoindolin-2-yl)propane-2-yloxy)ethylcarbamate as an off-white solid.

Workup

  1. customA 20 L 4-neck round-bottom flask was flushed with N2
  2. temperatureThe reaction mixture was cooled to 20˜30° C.
  3. stirringwith stirring
  4. stirringThe mixture was stirred for 30 minutes
  5. filtrationfiltered
  6. customThe filter cake was dried under vacuum at 60° C.

Sources & evidence

ORD record
ord-10af3905d98a46da91a625ef1ade0ad3
Source dataset
uspto-grants-2016_08
Patent number
US09402914B2

Reaction notes

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