Beta-Alanine → 2,5-dioxopyrrolidin-1-yl 3-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)propanoate

HRID 2280243Notes

Reaction equation

HRID 2280243 reaction equation
[NH2:1][CH2:2][CH2:3][C:4]([OH:6])=[O:5].[C:7]1(=O)[O:12][C:10](=[O:11])[CH:9]=[CH:8]1.O[N:15]1[C:19](=[O:20])[CH2:18][CH2:17][C:16]1=[O:21].C1(N=C=NC2CCCCC2)CCCCC1>CN(C=O)C>[C:7]1(=[O:12])[N:1]([CH2:2][CH2:3][C:4]([O:6][N:15]2[C:19](=[O:20])[CH2:18][CH2:17][C:16]2=[O:21])=[O:5])[C:10](=[O:11])[CH:9]=[CH:8]1

Participants

6

Reactant 4

HCID 239Beta-AlanineHCID 7923Maleic AnhydrideHCID 10868DicyclohexylcarbodiimideHCID 80170N-Hydroxysuccinimide

Product 1

HCID 46205972,5-dioxopyrrolidin-1-yl 3-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)propanoateYield 55%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of β-alanine (1.8 g, 20 mmol) and maleic anhydride (2 g, 20 mmol) in DMF (30 mL) was stirred at room temperature for 3 h. After the solid was completely dissolved, N-hydroxysuccinimide (NHS; 2.3 g, 20 mmol) and dicyclohexylcarbodiimide (DCC; 4.6 g, 24 mmol) was added into the solution and the mixture was stirred at room temperature overnight. The solution was filtered and the precipitate was washed with water (100 ml) and dichloromethane (100 ml). The filtrate was collected and the organic layer was washed with 3×50 ml 5% NaHCO3 and one time with brine. The organic layer was dried with Na2SO4 and dichloromethane removed under reduced pressure to obtain a white solid (55%). This solid does not need further purification and can be directly used for next coupling step. 1H NMR (CDCl3, 400 MHz): δ 2.82 (s, 4H, two succinimido-CH2), 3.02 (t, J=7.0 Hz, 2H, COCH2), 3.94 (t, J=7.0 Hz, 2H, NCH2), 6.74 (s, 2H, two CH).

Workup

  1. dissolutionAfter the solid was completely dissolved
  2. filtrationThe solution was filtered
  3. washthe precipitate was washed with water (100 ml) and dichloromethane (100 ml)
  4. customThe filtrate was collected
  5. washthe organic layer was washed with 3×50 ml 5% NaHCO3 and one time with brine
  6. dry with materialThe organic layer was dried with Na2SO4 and dichloromethane
  7. customremoved under reduced pressure

Sources & evidence

ORD record
ord-eb871bf9d8534fbfbc4bd577db4aa7d3
Source dataset
uspto-grants-2015_09
Patent number
US09138495B2

Reaction notes

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