Potassium Phosphate, Tribasic → 1-[5-(2-Ethoxy-2-oxoethoxy)-6-nitropyridin-2-yl]-5-oxopyrrolidin-3-carboxylic acid methyl ester

HRID 1847006Notes

Reaction equation

HRID 1847006 reaction equation
[CH3:1][O:2][C:3]([CH:5]1[CH2:9][C:8](=[O:10])[NH:7][CH2:6]1)=[O:4].[CH2:11]([O:13][C:14](=[O:27])[CH2:15][O:16][C:17]1[C:18]([N+:24]([O-:26])=[O:25])=[N:19][C:20](Br)=[CH:21][CH:22]=1)[CH3:12].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(OCC)(=O)C.O1CCOCC1>[CH3:1][O:2][C:3]([CH:5]1[CH2:9][C:8](=[O:10])[N:7]([C:20]2[CH:21]=[CH:22][C:17]([O:16][CH2:15][C:14]([O:13][CH2:11][CH3:12])=[O:27])=[C:18]([N+:24]([O-:26])=[O:25])[N:19]=2)[CH2:6]1)=[O:4]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 634876Binap, (A+-)-HCID 131181175-Oxo-pyrrolidine-3-carboxylic acid methyl esterHCID 59560649Ethyl (6-bromo-2-nitropyridin-3-yloxy)acetate

Product 1

HCID 867249371-[5-(2-Ethoxy-2-oxoethoxy)-6-nitropyridin-2-yl]-5-oxopyrrolidin-3-carboxylic acid methyl esterYield 76%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 5-oxopyrrolidin-3-carboxylic acid methyl ester (synthesized with reference to Tetrahedron Asymmetry, 2001, vol. 12, pages 3241-3250; 1.0 g, 6.99 mmol), [(6-bromo-2-nitropyridin-3-yl)oxy]acetic acid ethyl ester (synthesized with reference to WO2004/2992; 2.13 g, 6.99 mmol), palladium acetate (157 mg, 0.699 mmol), 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (417 mg, 0.699 mmol), potassium phosphate (4.83 g, 21 mmol) and 1,4-dioxane (50 ml) was stirred under a stream of nitrogen gas at 100° C. for 5 hours. After cooling, ethyl acetate was added to the reaction solution, the insoluble material was removed by filtration, the obtained filtrate was washed with water and saturated sodium chloride solution, dried over anhydrous magnesium sulfate and the solvent was removed under reduced pressure. The obtained residue was purified by silica gel column chromatography (n-hexane/ethyl acetate) to yield 1.95 g (76%) of the title compound in the form of a light brown syrup.

Workup

  1. temperatureAfter cooling
  2. customthe insoluble material was removed by filtration
  3. washthe obtained filtrate was washed with water and saturated sodium chloride solution
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customthe solvent was removed under reduced pressure
  6. customThe obtained residue was purified by silica gel column chromatography (n-hexane/ethyl acetate)

Sources & evidence

ORD record
ord-d59a187d977f4f00a690996215fd943f
Source dataset
uspto-grants-2015_02
Patent number
US08952010B2

Reaction notes

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