Sodium hydride → 1-{2-[(6-Bromopyridin-3-yl)oxy]ethyl}pyrrolidine-2,5-dione

HRID 1896711Notes

Reaction equation

HRID 1896711 reaction equation
[OH:1][C:2]1[CH:3]=[N:4][C:5]([Br:8])=[CH:6][CH:7]=1.[H-].[Na+].[O:11]=[C:12]1[CH2:16][CH2:15][C:14](=[O:17])[N:13]1[CH2:18][CH2:19]OS(C)(=O)=O>CN(C=O)C.CN(C)C1C=CN=CC=1>[Br:8][C:5]1[N:4]=[CH:3][C:2]([O:1][CH2:19][CH2:18][N:13]2[C:14](=[O:17])[CH2:15][CH2:16][C:12]2=[O:11])=[CH:7][CH:6]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 27628652-Bromo-5-hydroxypyridineHCID 100822242,5-Pyrrolidinedione, 1-[2-[(methylsulfonyl)oxy]ethyl]-

Product 1

HCID 714277691-{2-[(6-Bromopyridin-3-yl)oxy]ethyl}pyrrolidine-2,5-dioneYield 62.3%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

10 g (58 mmol) of 3-hydroxy-6-bromopyridine were dissolved in 40 ml of DMF and treated with 2.76 g (69 mmol) of sodium hydride (60% suspension in mineral oil). After stirring at room temperature for 1 h, 20 mg of 4-dimethylaminopyridine were added and the mixture was treated with 16.53 g (74.8 mmol) of methanesulfonic acid 2-(2,5-dioxopyrrolidin-1-yl)ethyl ester and heated to 100° C. for 3 h. Subsequently, the solvent was evaporated and the residue was taken up in water and extracted 4 times with ethyl acetate. The combined organic phases were dried and evaporated to dryness. The remaining material was purified by chromatography (silica gel, dichloromethane/methanol 98:2) followed by preparative HPLC (RP18, acetonitrile/water containing 0.1% TFA) to yield 10.8 g of the title compound.

Workup

  1. temperatureheated to 100° C. for 3 h
  2. customSubsequently, the solvent was evaporated
  3. extractionextracted 4 times with ethyl acetate
  4. customThe combined organic phases were dried
  5. customevaporated to dryness
  6. customThe remaining material was purified by chromatography (silica gel, dichloromethane/methanol 98:2)

Sources & evidence

ORD record
ord-7678fb527e954848a3a1975d884bd17c
Source dataset
uspto-grants-2013_08
Patent number
US08518976B2

Reaction notes

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