Potassium Phosphate, Tribasic → [(6-{(4S)-4-[(tert-Butoxycarbonyl)amino]-2-oxopyrrolidin-1-yl}-2-nitropyridin-3-yl)oxy]acetic acid ethyl ester

HRID 1847011Notes

Reaction equation

HRID 1847011 reaction equation
[C:1]([O:5][C:6](=[O:14])[NH:7][C@H:8]1[CH2:12][C:11](=[O:13])[NH:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[CH2:15]([O:17][C:18](=[O:31])[CH2:19][O:20][C:21]1[C:22]([N+:28]([O-:30])=[O:29])=[N:23][C:24](Br)=[CH:25][CH:26]=1)[CH3:16].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>[CH2:15]([O:17][C:18](=[O:31])[CH2:19][O:20][C:21]1[C:22]([N+:28]([O-:30])=[O:29])=[N:23][C:24]([N:10]2[CH2:9][C@@H:8]([NH:7][C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:14])[CH2:12][C:11]2=[O:13])=[CH:25][CH:26]=1)[CH3:16]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 634876Binap, (A+-)-HCID 45091936(S)-tert-Butyl (5-oxopyrrolidin-3-yl)carbamateHCID 59560649Ethyl (6-bromo-2-nitropyridin-3-yloxy)acetate

Product 1

HCID 86724942[(6-{(4S)-4-[(tert-Butoxycarbonyl)amino]-2-oxopyrrolidin-1-yl}-2-nitropyridin-3-yl)oxy]acetic acid ethyl esterYield 36%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
100 °C

Procedure

A mixture of [(3S)-5-oxopyrrolidin-3-yl]carbamic acid tert-butyl ester (synthesized with reference to WO2004/22536; 505 mg, 2.52 mmol), [(6-bromo-2-nitropyridin-3-yl)oxy]acetic acid ethyl ester (synthesized with reference to WO2004/2992; 769 mg, 2.52 mmol), palladium acetate (56.6 mg, 0.252 mmol), 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (157 mg, 0.252 mmol), potassium phosphate (1.74 g, 7.56 mmol) and 1,4-dioxane (25 ml) was stirred under a stream of nitrogen gas at 100° C. for 6 hours. After cooling, ethyl acetate was added to the reaction solution to remove the insoluble material 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 380 mg (36%) of the title compound in the form of a light brown syrup.

Workup

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

Sources & evidence

ORD record
ord-d5878cece155496d9cc057c9a2ddee51
Source dataset
uspto-grants-2015_02
Patent number
US08952010B2

Reaction notes

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