Ethyl Glycolate → Ethyl 2-((5-bromo-3-nitropyridin-2-yl)oxy)acetate

HRID 1509336Notes

Reaction equation

HRID 1509336 reaction equation
[H-].[Na+].[C:3]([O:7][CH2:8][CH3:9])(=[O:6])[CH2:4][OH:5].[Br:10][C:11]1[CH:12]=[C:13]([N+:18]([O-:20])=[O:19])[C:14](Cl)=[N:15][CH:16]=1.[H-].[Na+].C(OCC)(=O)CO>O1CCOCC1>[Br:10][C:11]1[CH:12]=[C:13]([N+:18]([O-:20])=[O:19])[C:14]([O:5][CH2:4][C:3]([O:7][CH2:8][CH3:9])=[O:6])=[N:15][CH:16]=1

Participants

6

Reactant 4

HCID 12184Ethyl GlycolateHCID 24758Sodium hydrideHCID 70194125-Bromo-2-chloro-3-nitropyridineHCID 86683686HCID 86683686, compound

Product 1

HCID 4647502Ethyl 2-((5-bromo-3-nitropyridin-2-yl)oxy)acetateYield 44%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

To a suspension of sodium hydride (5.31 g, 133 mmol) in 1,4-dioxane (250 mL) was added drop wise ethyl glycolate (12.56 ml, 133 mmol) over a period of 30 minutes ensuring that the temperature was maintained below 30° C. The resulting thick suspension was stirred at room temperature for 15 minutes. In a separate 1 L round-bottomed flask was added 5-bromo-2-chloro-3-nitropyridine (21 g, 88 mmol) in 1,4-dioxane (150 mL) to give a brown solution. The sodium hydride/ethyl glycolate slurry was added drop wise over a period of 30 minutes. The resulting reaction mixture was heated to 80° C. overnight. The reaction mixture was concentrated under reduced pressure and the residue was purified via Biotage chromatography (silica 340 g column, gradient elution from 0% to 10% ethyl acetate in cyclohexane) to give a pale yellow solid (11.8 g, 43% yield). 1H NMR (500 MHz, CDCl3): 8.48 (1H, d), 8.42 (1H, d), 5.07 (2H, s), 4.25 (2H, q), 1.30 (3H, s).

Workup

  1. temperaturewas maintained below 30° C
  2. customto give a brown solution
  3. customThe resulting reaction mixture
  4. temperaturewas heated to 80° C. overnight
  5. concentrationThe reaction mixture was concentrated under reduced pressure
  6. customthe residue was purified via Biotage chromatography (silica 340 g column, gradient elution from 0% to 10% ethyl acetate in cyclohexane)

Sources & evidence

ORD record
ord-d3b64bdd172e441dbc8fef075078d864
Source dataset
uspto-grants-2015_12
Patent number
US09221838B2

Reaction notes

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