Dimethylformamide → 7-(3-(1,3-Dioxo-1,3-dihydroisoindol-2-yl)propoxy)-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione

HRID 1183084Notes

Reaction equation

HRID 1183084 reaction equation
C(=O)([O-])[O-].[K+].[K+].Br[CH2:8][CH2:9][CH2:10][N:11]1[C:15](=[O:16])[C:14]2=[CH:17][CH:18]=[CH:19][CH:20]=[C:13]2[C:12]1=[O:21].CN(C=O)C.[CH2:27]([N:29]1[C:35](=[O:36])[C:34]([CH3:38])([CH3:37])[C:33](=[O:39])[N:32]([CH3:40])[C:31]2[CH:41]=[C:42]([OH:45])[CH:43]=[CH:44][C:30]1=2)[CH3:28]>C(OCC)(=O)C.O>[O:21]=[C:12]1[C:13]2[C:14](=[CH:17][CH:18]=[CH:19][CH:20]=2)[C:15](=[O:16])[N:11]1[CH2:10][CH2:9][CH2:8][O:45][C:42]1[CH:43]=[CH:44][C:30]2[N:29]([CH2:27][CH3:28])[C:35](=[O:36])[C:34]([CH3:37])([CH3:38])[C:33](=[O:39])[N:32]([CH3:40])[C:31]=2[CH:41]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 21611N-3-BromopropylphthalimideHCID 686733851-Ethyl-7-hydroxy-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione

Product 1

HCID 686733627-(3-(1,3-Dioxo-1,3-dihydroisoindol-2-yl)propoxy)-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dioneYield 83.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

Potassium carbonate (2.99 g, 21.6 mmol) and N-(3-bromopropyl)phthalimide (2.32 g, 8.65 mmol) were added to a DMF solution (50 ml) of 1-ethyl-7-hydroxy-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione (1.89 g, 7.2 mmol), and stirred at room temperature overnight. Water was added to the reaction mixture, and extraction with ethyl acetate was performed. The organic layer was washed with water and a saturated sodium chloride aqueous solution, in this order. The organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=2:1→3:7). The purified product was concentrated to dryness under reduced pressure to thereby obtain 2.70 g (yield: 83%) of 7-(3-(1,3-dioxo-1,3-dihydroisoindol-2-yl)propoxy)-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione as a white powder.

Workup

  1. washThe organic layer was washed with water
  2. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=2:1→3:7)
  5. concentrationThe purified product was concentrated to dryness under reduced pressure

Sources & evidence

ORD record
ord-bfebe6aaafef4a8388cc54f000ba1816
Source dataset
uspto-grants-2014_03
Patent number
US08664217B2

Reaction notes

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