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

HRID 82292Notes

Reaction equation

HRID 82292 reaction equation
I[C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][N:3]=1.[C:9]([O:17][CH2:18][CH3:19])(=[O:16])[CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12].C(=O)([O-])[O-].[Cs+].[Cs+].N1C=CC=CC=1C(O)=O>O1CCOCC1.[Cu]I>[CH2:14]([O:13][C:11](=[O:12])[CH:10]([C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][N:3]=1)[C:9]([O:17][CH2:18][CH3:19])=[O:16])[CH3:15]

Participants

7

Reactant 4

HCID 1018Picolinic acidHCID 7761Diethyl MalonateHCID 10796Cesium carbonateHCID 117361162-Iodo-5-methylpyridine

Product 1

HCID 57910103Diethyl 2-(5-methylpyridin-2-yl)malonateYield 23%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 312751,4-DioxaneSolvent

Procedure

To a stirred solution of 2-Iodo-5-methyl-pyridine (Preparation 272, 1 g, 4.57 mmol) and diethyl malonate (2.08 mL, 13.70 mmol) in anhydrous dioxane (12 mL) was added cesium carbonate (4.46 gm, 13.7 mmol) and the solution was degassed with argon for min. CuI (174 mg, 0.91 mmol) and picolinic acid (225 mg, 1.83 mmol) were added and the resultant mixture was heated in a sealed tube at 100° C. for 16 hours. The reaction mixture was cooled to room temperature, quenched with water (25 mL) and extracted with EtOAc (3×25 ml). The combined organic layers were washed with water (2×10 mL) and brine (10 mL), dried (Na2SO4) and evaporated in vacuo. The crude material was purified by column chromatography on silica gel (gradient of hexane:EtOAc 100:0 to 90:10) to afford the title compound as an oil in 23% yield, 300 mg.

Workup

  1. customthe solution was degassed with argon for min
  2. customquenched with water (25 mL)
  3. extractionextracted with EtOAc (3×25 ml)
  4. washThe combined organic layers were washed with water (2×10 mL) and brine (10 mL)
  5. dry with materialdried (Na2SO4)
  6. customevaporated in vacuo
  7. customThe crude material was purified by column chromatography on silica gel (gradient of hexane:EtOAc 100:0 to 90:10)

Sources & evidence

ORD record
ord-86545ff1f59b4bd4ab0cb1f6580c6218
Source dataset
uspto-grants-2014_09
Patent number
US08846698B2

Reaction notes

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