Picolinic acid → Diethyl (pyridin-2-yl)propanedioate

HRID 81070

Reaction equation

HRID 81070 reaction equation
I[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.N1C=CC=CC=1C(O)=O.C(=O)([O-])[O-].[Cs+].[Cs+].[C:23]([O:31][CH2:32][CH3:33])(=[O:30])[CH2:24][C:25]([O:27][CH2:28][CH3:29])=[O:26]>O1CCOCC1.C(OCC)(=O)C.[Cu]I>[N:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[CH:24]([C:25]([O:27][CH2:28][CH3:29])=[O:26])[C:23]([O:31][CH2:32][CH3:33])=[O:30]

Participants

8

Reactant 4

HCID 1018Picolinic acidHCID 7761Diethyl MalonateHCID 10796Cesium carbonateHCID 2211262-Iodopyridine

Product 1

HCID 331545Diethyl (pyridin-2-yl)propanedioateYield 60.5%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 2-iodopyridine (1.00 g, 4.88 mmol), picolinic acid (0.060 g, 0.488 mmol), copper(I) iodide (0.046 g, 0.244 mmol), cesium carbonate (4.77 g, 14.63 mmol) and diethyl malonate (1.563 g, 9.76 mmol) in dioxane (10 mL) was stirred under nitrogen at room temperature for 15 h. The mixture was diluted with ethyl acetate (200 mL), washed with saturated ammonium chloride (20 mL), water (20 mL), brine (20 mL), dried (MgSO4) and concentrated. Silica gel chromatography, loading with dichloromethane-hexanes (1:1) and eluting with 5 to 30% ethyl acetate in hexanes, gave diethyl 2-(pyridin-2-yl)malonate (700 mg, 42% yield). 1H NMR (400 MHz, CDCl3) δ ppm 8.58 (1H, δ, J=4.77 Hz), 7.71 (1H, dd, J=7.78, 1.51 Hz), 7.50 (1H, δ, J=7.78 Hz), 7.18-7.24 (1H, m), 4.94 (1H, s), 4.14-4.32 (4H, m, J=7.15, 7.15, 7.03, 3.51 Hz), 1.19-1.35 (6H, m); MS (ES+) m/z: 238 (M+H); LC retention time: 1.88 min (analytical HPLC Method A).

Workup

  1. washwashed with saturated ammonium chloride (20 mL), water (20 mL), brine (20 mL)
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated
  4. washeluting with 5 to 30% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-7a45419e5a7243959d4362c056890976
Source dataset
uspto-grants-2014_09
Patent number
US08846673B2

Linked notes

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