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

HRID 220200

Reaktionsgleichung

Reaktionsgleichung von HRID 220200
[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]

Komponenten

7

Edukt 4

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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 2

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

Versuchsvorschrift

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).

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-a0f0e68cae3740dab0a1c7d2c66551dc
Quelldatensatz
uspto-grants-2012_06
Patentnummer
US08202866B2

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