1,3-dihydro-1,3-dioxo-2H-isoindole-2-propionyl chloride → 1-(3-(1,3-Dioxoisoindolin-2-yl)propanoyl)-4,4-dimethylpyrrolidine-2-carboxylic acid

HRID 520306Notes

Reaction equation

HRID 520306 reaction equation
[CH3:1][C:2]1([CH3:10])[CH2:6][NH:5][CH:4]([C:7]([OH:9])=[O:8])[CH2:3]1.[O:11]=[C:12]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[C:14](=[O:21])[N:13]1[CH2:22][CH2:23][C:24](Cl)=[O:25]>CN(C=O)C>[O:11]=[C:12]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[C:14](=[O:21])[N:13]1[CH2:22][CH2:23][C:24]([N:5]1[CH2:6][C:2]([CH3:10])([CH3:1])[CH2:3][CH:4]1[C:7]([OH:9])=[O:8])=[O:25]

Participants

4

Reactant 2

HCID 869661,3-dihydro-1,3-dioxo-2H-isoindole-2-propionyl chlorideHCID 2866424,4-Dimethylpyrrolidine-2-carboxylic acid

Product 1

HCID 1177774051-(3-(1,3-Dioxoisoindolin-2-yl)propanoyl)-4,4-dimethylpyrrolidine-2-carboxylic acid

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4,4-dimethylpyrrolidine-2-carboxylic acid 137f (13.0 g, 72.5 mmol) in DMF (250 mL) was added 137h (17.0 g, 72.5 mmol) and TEA (14.5 g, 145 mmol). See FIG. 2. The mixture was stirred at RT (room temperature) for 16 h (sixteen hours). Upon reaction completion, the mixture was washed with brine (50 mL×3), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to give crude 1-(3-(1,3-dioxoisoindolin-2-yl)propanoyl)-4,4-dimethylpyrrolidine-2-carboxylic acid 137i, which was used directly without purification.

Workup

  1. customUpon reaction completion
  2. washthe mixture was washed with brine (50 mL×3)
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-adb298f8946e41fbbb0ca163a4ad0259
Source dataset
uspto-grants-2016_05
Patent number
US09326985B2

Reaction notes

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