Triphenylphosphine → Ethyl 2-((3-nitro-5-phenylpyridin-2-yl)oxy)acetate

HRID 1509272Notes

Reaction equation

HRID 1509272 reaction equation
Br[C:2]1[CH:3]=[C:4]([N+:15]([O-:17])=[O:16])[C:5]([O:8][CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])=[N:6][CH:7]=1.[C:18]1(B(O)O)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[F-].[Cs+]>COCCOC.ClCCl.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[N+:15]([C:4]1[C:5]([O:8][CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])=[N:6][CH:7]=[C:2]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:3]=1)([O-:17])=[O:16]

Participants

8

Reactant 4

HCID 11776TriphenylphosphineHCID 25953Cesium fluorideHCID 66827Phenylboronic AcidHCID 4647502Ethyl 2-((5-bromo-3-nitropyridin-2-yl)oxy)acetate

Product 1

HCID 67255179Ethyl 2-((3-nitro-5-phenylpyridin-2-yl)oxy)acetateYield 38%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6344DichloromethaneSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
75 °C

Procedure

In a 1 l round-bottomed flask was added ethyl 2-(5-bromo-3-nitropyridin-2-yloxy)acetate (18.33 g, 60.1 mmol), phenylboronic acid (10.99 g, 90 mmol), triphenylphosphine (4.73 g, 18.02 mmol) and cesium fluoride (45.6 g, 300 mmol) in 1,2-dimethoxyethane (300 ml) to give a yellow solution. The reaction mixture was degassed by bubbling nitrogen for 30 minutes. Palladium(II)acetate (2.023 g, 9.01 mmol) was added and the mixture was heated to 75° C. under a nitrogen atmosphere overnight. The reaction mixture was allowed to cool to room temperature and concentrated to dryness under reduced pressure to give a brown solid. This was re-dissolved in dichloromethane, filtered and concentrated to dryness under reduced pressure to give a brown solid The crude residue was purified via Biotage chromatography (gradient 5% to 60% ethyl acetate in n-hexanes) to give the title compound (6.9 g, 38%). 1H NMR (500 MHz, CDCl3) δ 8.58 (1H, s), 8.56 (1H, s), 7.59-7.52 (2H, m), 7.48-7.46 (2H, m), 7.45-7.43 (1H, m), 5.13 (2H, s), 4.30-4.26 (2H, q), 1.33-1.30 (3H, t).

Workup

  1. customto give a yellow solution
  2. customThe reaction mixture was degassed
  3. customby bubbling nitrogen for 30 minutes
  4. temperatureto cool to room temperature
  5. concentrationconcentrated to dryness under reduced pressure
  6. customto give a brown solid
  7. filtrationfiltered
  8. concentrationconcentrated to dryness under reduced pressure
  9. customto give a brown solid The crude residue
  10. customwas purified via Biotage chromatography (gradient 5% to 60% ethyl acetate in n-hexanes)

Sources & evidence

ORD record
ord-59c1898b21b748b9854d257a0fe3b009
Source dataset
uspto-grants-2015_12
Patent number
US09221838B2

Reaction notes

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