Picolinic acid → Diethyl 2-(5-bromopyridin-2-yl)malonate

HRID 1753081Notes

Reaction equation

HRID 1753081 reaction equation
I[C:2]1[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][N:3]=1.C([C:11](CC)([C:15]([O-:17])=[O:16])[C:12]([O-:14])=[O:13])C.C(=O)([O-])[O-].[Cs+].[Cs+].N1C=CC=[CH:28][C:27]=1C(O)=O.O1CCO[CH2:37][CH2:36]1>[Cu](I)I>[CH2:27]([O:17][C:15](=[O:16])[CH:11]([C:2]1[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][N:3]=1)[C:12]([O:14][CH2:36][CH3:37])=[O:13])[CH3:28]

Participants

7

Reactant 5

HCID 1018Picolinic acidHCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 5936905-Bromo-2-iodopyridineHCID 69515632,2-Diethylpropanedioate

Product 1

HCID 59238270Diethyl 2-(5-bromopyridin-2-yl)malonate

Reagents, catalysts & solvents 1

HCID 83717Copper iodideCatalyst

Conditions

Temperature
80 °C

Procedure

To a suspension of 2-iodo-5-bromopyridine (2.0 g, 7.06 mmol), diethylmalonate (2.12 mL, 14.12 mmol) and cesium carbonate (6.88 g, 21.18 mmol) in dioxane (20 mL) was added copper iodide (268 mg, 1.41 mmol) followed by picolinic acid (346 mg, 2.82 mmol) and the reaction was heated to 80° C. for 16 hours. The reaction was cooled, filtered and the filtrate was concentrated in vacuo. The residue was diluted with EtOAc, washed with water, brine, dried over sodium sulphate and concentrated in vacuo. The residue was purified using silica gel column chromatography eluting with 2% EtOAc in hexanes to afford the title compound that was used directly in the next reaction.

Workup

  1. temperatureThe reaction was cooled
  2. filtrationfiltered
  3. concentrationthe filtrate was concentrated in vacuo
  4. additionThe residue was diluted with EtOAc
  5. washwashed with water, brine
  6. dry with materialdried over sodium sulphate
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified
  9. washeluting with 2% EtOAc in hexanes

Sources & evidence

ORD record
ord-b95872acc08b44a0a9bedea70248060d
Source dataset
uspto-grants-2015_10
Patent number
US09163021B2

Reaction notes

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