Cesium fluoride → 1-benzyl-3-p-tolyl-1H-pyrrole-2,5-dione

HRID 538695Notes

Reaction equation

HRID 538695 reaction equation
[CH2:1]([N:8]1[C:12](=[O:13])[CH:11]=[C:10](Br)[C:9]1=[O:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.B(O)(O)[C:17]1[CH:18]=[CH:19][C:20]([CH3:23])=[CH:21][CH:22]=1.[F-].[Cs+]>O1CCOCC1.C(Cl)Cl>[CH2:1]([N:8]1[C:12](=[O:13])[CH:11]=[C:10]([C:17]2[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][CH:18]=2)[C:9]1=[O:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 25953Cesium fluorideHCID 79799Tolylboronic acidHCID 156289041-benzyl-3-bromo-2,5-dihydro-1H-pyrrole-2,5-dione

Product 1

HCID 706902091-benzyl-3-p-tolyl-1H-pyrrole-2,5-dione

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

A solution of bromomaleic anhydride (1 g, 5.7 mmol) and benzyl amine (0.7 mL, 6.8 mmol) in acetic acid (15 mL) was warmed to 50° C. and stirred overnight. The reaction was then cooled to room temperature, diluted with CH2Cl2 (50 mL) and washed with NaHCO3 (3×25 mL) and brine (25 mL). The organic layer was then dried (MgSO4), filtered and the solvent removed under reduced pressure. The residue was purified using gradient flash chromatography (0-100% ethyl acetate in pet ether) to provide 1-benzyl-3-bromo-1H-pyrrole-2,5-dione (18). 1H NMR (400 MHz, CDCl3) δ 4.71 (s, 2H), 6.87 (s, 2H), 7.26-7.37 (m, 5H). A stirred solution of 1-benzyl-3-bromo-1H-pyrrole-2,5-dione (0.26 g, 1.0 mmol) and p-tolylboronic acid (0.16 g, 1.2 mmol) in dioxane (10 mL) was degassed with a stream of nitrogen for 10 minutes before being treated with CsF (0.39 g, 2.6 mmol) and C12Pd(dppf).CH2Cl2 (0.05 g, 0.06 mmol). The reaction was stirred at room temperature for 1 h then warmed to 40° C. for 1 h. The mixture was then cooled, diluted with CH2Cl2 (30 mL) and filtered through a pad of celite. The filtrate was concentrated under reduced pressure and purified using gradient flash chromatography (0-10% ethyl acetate in pet ether) to provide the title compound 15.

Workup

  1. temperaturethen warmed to 40° C. for 1 h
  2. temperatureThe mixture was then cooled
  3. filtrationfiltered through a pad of celite
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. custompurified

Sources & evidence

ORD record
ord-0ea92519bde54ebea35e0510eff83818
Source dataset
uspto-grants-2014_10
Patent number
US08865750B2

Reaction notes

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