Silane, ((1-methoxy-2-methyl-1-propenyl)oxy)trimethyl- → 2-Methyl-2-(6-nitropyridin-3-yl)-propionic acid methyl ester

HRID 2069720Notes

Reaction equation

HRID 2069720 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([N+:8]([O-:10])=[O:9])=[N:6][CH:7]=1.[CH3:11][O:12][C:13]([O:17][Si](C)(C)C)=[C:14]([CH3:16])[CH3:15]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[F-].[Zn+2].[F-]>[CH3:11][O:12][C:13](=[O:17])[C:14]([CH3:16])([C:2]1[CH:7]=[N:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=1)[CH3:15]

Participants

5

Reactant 2

HCID 552336Silane, ((1-methoxy-2-methyl-1-propenyl)oxy)trimethyl-HCID 8176205-Bromo-2-nitropyridine

Product 1

HCID 594738022-Methyl-2-(6-nitropyridin-3-yl)-propionic acid methyl esterYield 24%

Reagents, catalysts & solvents 2

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 10129912Zinc(II) fluorideCatalyst

Procedure

5-Bromo-2-nitro-pyridine (7.0 g, 35 mmol), (1-methoxy-2-methyl-propenyloxy)-trimethyl-silane (12.0 g, 69 mmol), bis(dibenzylideneacetone)palladium (1.0 g, 1.75 mmol), and zinc fluoride (1.8 g, 17.5 mmol) were added to a round bottom flask and purged with nitrogen. Tri-tert-butylphosphine (3.5 ml of a 1.0 M solution in toluene) and 140 ml of DMF were added by syringe. The reaction mixture was heated at 80 degrees centigrade overnight. The reaction was diluted with ethyl acetate, water was added, and the layers were separated. The organic layer was washed with water and brine, dried and concentrated. The crude product was purified by flash chromatography using a gradient of 0% to 15% ethyl acetate in hexanes to yield 1.88 g (24%) of 2-methyl-2-(6-nitropyridin-3-yl)-propionic acid methyl ester.

Workup

  1. custompurged with nitrogen
  2. additionTri-tert-butylphosphine (3.5 ml of a 1.0 M solution in toluene) and 140 ml of DMF were added by syringe
  3. temperatureThe reaction mixture was heated at 80 degrees centigrade overnight
  4. additionThe reaction was diluted with ethyl acetate, water
  5. additionwas added
  6. customthe layers were separated
  7. washThe organic layer was washed with water and brine
  8. customdried
  9. concentrationconcentrated
  10. customThe crude product was purified by flash chromatography

Sources & evidence

ORD record
ord-8f50b0a678aa4714a7a1f2827cb09ff9
Source dataset
uspto-grants-2012_10
Patent number
US08299077B2

Reaction notes

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