N,N'-Dimethylethylenediamine → HCID 86724982, compound

HRID 1847057Notes

Reaction equation

HRID 1847057 reaction equation
[Si:1]([O:8][CH2:9][C@H:10]1[CH2:14][NH:13][C:12](=[O:15])[CH2:11]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[CH2:16]([O:18][C:19](=[O:32])[CH2:20][O:21][C:22]1[C:23]([N+:29]([O-:31])=[O:30])=[N:24][C:25](Br)=[CH:26][CH:27]=1)[CH3:17].C(=O)([O-])[O-].[K+].[K+].CNCCNC>[Cu]I.C(OCC)(=O)C.C1(C)C=CC=CC=1>[CH2:16]([O:18][C:19](=[O:32])[CH2:20][O:21][C:22]1[C:23]([N+:29]([O-:31])=[O:30])=[N:24][C:25]([N:13]2[CH2:14][C@H:10]([CH2:9][O:8][Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2])[CH2:11][C:12]2=[O:15])=[CH:26][CH:27]=1)[CH3:17]

Participants

8

Reactant 4

HCID 8070N,N'-Dimethylethylenediamine2×HCID 11430Potassium CarbonateHCID 59560649Ethyl (6-bromo-2-nitropyridin-3-yloxy)acetate3×HCID 86724981HCID 86724981, compound

Product 1

HCID 86724982HCID 86724982, compoundYield 71%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst2×HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of (4R)-4-({[tert-butyl(dimethyl)silyl]oxy}methyl)pyrrolidin-2-one (1.93 g, 8.43 mmol), [(6-bromo-2-nitropyridin-3-yl)oxy]acetic acid ethyl ester (synthesized with reference to WO2004/2992, 2.57 g, 8.43 mmol), potassium carbonate (2.33 g, 16.9 mmol), copper (I) iodide (803 mg, 4.21 mmol), N,N′-dimethylethylenediamine (0.449 ml, 4.21 mmol) and toluene (40 ml) was stirred at 100° C. for 8 hours under a stream of nitrogen gas. [(6-Bromo-2-nitropyridin-3-yl)oxy]acetic acid ethyl ester (1.29 g, 4.21 mmol) was added thereto and stirred overnight at 100° C. [(6-Bromo-2-nitropyridin-3-yl)oxy]acetic acid ethyl ester (1.29 g, 4.21 mmol), copper (I) iodide (803 mg, 4.21 mmol) and N,N′-dimethylethylenediamine (0.449 ml, 4.21 mmol) were further added thereto which was stirred at 100° C. for 24 hours. After cooling, ethyl acetate was added to the reaction solution to remove the insoluble material by filtration and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (n-hexane/ethyl acetate), thereby obtaining 2.70 g (71%) of ({6-[(4R)-4-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2-oxopyrrolidin-1-yl]-2-nitropyridin-3-yl}oxy)acetic acid ethyl ester in the form of a reddish brown gummy solid. The whole amount was dissolved in acetic acid (18 ml) to which reduced iron (999 mg, 17.9 mmol) was added and the mixture was stirred at 60° C. for 3 hours. After cooling, a mixed solution of chloroform-methanol (9:1) was added to remove the insoluble material by filtration and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform/methanol) to yield 1.93 g (86%) of the title compound in the form of a yellow solid.

Workup

  1. additionwere further added
  2. stirringwhich was stirred at 100° C. for 24 hours
  3. temperatureAfter cooling
  4. customto remove the insoluble material
  5. filtrationby filtration
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customThe obtained residue was purified by silica gel column chromatography (n-hexane/ethyl acetate)

Sources & evidence

ORD record
ord-cbd486215b9940048e41a3849dfe5fcc
Source dataset
uspto-grants-2015_02
Patent number
US08952010B2

Reaction notes

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