Ethyl Methacrylate → ethyl (E)-3-(6-aminopyridin-3-yl)-2-methylacrylate

HRID 2112660Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2112660
[NH2:1][C:2]1[CH:7]=[CH:6][C:5](Br)=[CH:4][N:3]=1.[C:9]([O:14][CH2:15][CH3:16])(=[O:13])[C:10]([CH3:12])=[CH2:11].CCN(C(C)C)C(C)C.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>C(#N)CC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[NH2:1][C:2]1[N:3]=[CH:4][C:5](/[CH:11]=[C:10](\[CH3:12])/[C:9]([O:14][CH2:15][CH3:16])=[O:13])=[CH:6][CH:7]=1

Komponenten

7

Edukt 4

HCID 7343Ethyl MethacrylateHCID 706222-Amino-5-bromopyridineHCID 80271Tri-o-tolylphosphineHCID 81531Diisopropylethylamine

Produkt 1

HCID 57440844ethyl (E)-3-(6-aminopyridin-3-yl)-2-methylacrylateAusbeute 37,3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 167845palladium(II) acetateKatalysatorHCID 7854PropionitrileLösungsmittel

Versuchsvorschrift

To a stirred solution of 2-amino-5-bromopyridine (25 g, 140 mmole) in propionitrile (150 mL) was added ethyl methacrylate (50 mL, 400 mmole), DIEA (50 mL, 287 mmole), palladium(II) acetate (1.57 g, 7 mmole), and tri-o-tolylphosphine (4.3 g, 14 mmole). The reaction was purged with argon and heated at reflux for 6 hr, then was cooled to RT and concentrated to dryness under vacuum. The residue was taken up in 80% ethyl acetate/hexanes (100 mL), and the solution was filtered through a pad of silica gel, eluting with 80% ethyl acetate/hexanes (400 mL) until all the product was eluted off. The yellowish filtrate was concentrated under vacuum, and the residue was taken up in a small volume of 1:1 Et2O/petroleum ether. The precipitate which formed was collected and dried under vacuum to give ethyl (E)-3-(6-aminopyridin-3-yl)-2-methylacrylate (10.77 g, 37%) as a pale yellow solid: LCMS (ES) m/e 207.0 (M+H)+; 1H NMR (300 MHz, CDCl3) δ 8.05 (d, J=1.7 Hz, 1H), 7.63 (dd, 1H), 7.48 (s, 1H), 6.75 (d, J=8.8 Hz, 1H), 5.79 (br s, 2H), 4.26 (q, 2H), 2.10 (s, 3H), 1.34 (t, 3H). The filtrate was concentrated to dryness and purified by flash chromatography on silica gel (4:1 ethyl acetate/hexanes) to give additional ethyl (E)-3-(6-aminopyridin-3-yl)-2-methylacrylate (0.87 g, 3%) and ethyl 2-(6-aminopyridin-3-ylmethyl)acrylate (5.77 g, 20%) as a yellow oil: LCMS (ES) m/e 207.0 (M+H)+; 1H NMR (300 MHz, CDCl3) δ 7.86 (d, J=2.1 Hz, 1H), 7.32 (dd, 1H), 6.53 (d, J=8.5 Hz, 1H), 6.21 (d, J=1.8 Hz, 1H), 5.48 (d, J=1.4 Hz, 1H), 4.17 (q, 2H), 3.47 (s, 2H), 1.27 (t, 3H).

Aufarbeitung

  1. customThe reaction was purged with argon
  2. temperatureheated
  3. temperatureat reflux for 6 hr
  4. concentrationconcentrated to dryness under vacuum
  5. filtrationthe solution was filtered through a pad of silica gel
  6. washeluting with 80% ethyl acetate/hexanes (400 mL) until all the product
  7. washwas eluted off
  8. concentrationThe yellowish filtrate was concentrated under vacuum
  9. customThe precipitate which formed
  10. customwas collected
  11. customdried under vacuum

Quellen und Nachweise

ORD-Eintrag
ord-17de5791fc664d4a92caf76bedb39a13
Quelldatensatz
uspto-grants-2009_04
Patentnummer
US07524843B2

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