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

HRID 220200

Reaction equation

HRID 220200 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5](I)=[N:6][CH:7]=1.[CH2:9]([O:11][C:12](=[O:19])[CH2:13][C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH3:10].C([O-])([O-])=O.[Cs+].[Cs+].N1C=CC=CC=1C(O)=O>O1CCOCC1.[Cu]I>[CH2:9]([O:11][C:12](=[O:19])[CH:13]([C:5]1[CH:4]=[CH:3][C:2]([Br:1])=[CH:7][N:6]=1)[C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH3:10]

Participants

7

Reactant 4

HCID 1018Picolinic acidHCID 7761Diethyl MalonateHCID 10796Cesium carbonateHCID 5936905-Bromo-2-iodopyridine

Product 1

HCID 59238270Diethyl 2-(5-bromopyridin-2-yl)malonateYield 50%

Reagents, catalysts & solvents 2

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

Procedure

A mixture of 5-bromo-2-iodo-pyridine (56.8 g, 0.2 mol), malonic acid diethyl ester (64 g, 0.4 mol), CuI (3.8 g, 0.02 mol), Cs2CO3 (195.5 g, 0.6 mol) and pyridine-2-carboxylic acid (2.46 g, 0.04 mol) in 1,4-dioxane (400 mL) was stirred at 70 degrees Celsius under N2 for 24 hours. After cooling to room temperature, the solid was filtered and the solvent was evaporated. The residue was dissolved in ethyl acetate (400 mL) and washed with water, brine, dried over Na2SO4, filtered, concentrated in vacuo, the crude product was purified by flash chromatography (Petroleum Ether:EtOAc=20:1) to obtain an oil (31.6 g, 50%). MS: calc'd 316 (MH+), exp 316 (MH+). 1H NMR (d6-DMSO, 400 MHz), 8.68 (d, 1H, J=2.4 Hz), 8.11 (dd, 1H, J=2.4, 8.4 Hz), 7.45 (d, 1H, J=8.4 Hz), 5.16 (s, 1H), 4.20-4.07 (m, 4H), 1.18 (t, J=8.4 Hz, 6H).

Workup

  1. filtrationthe solid was filtered
  2. customthe solvent was evaporated
  3. dissolutionThe residue was dissolved in ethyl acetate (400 mL)
  4. washwashed with water, brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customthe crude product was purified by flash chromatography (Petroleum Ether:EtOAc=20:1)

Sources & evidence

ORD record
ord-a0f0e68cae3740dab0a1c7d2c66551dc
Source dataset
uspto-grants-2012_06
Patent number
US08202866B2

Linked notes

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