Reaktion #304453

Reaktionsgleichung

2-chloro-5-fluoro-3-amino-pyridine

4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester

sodium carbonate

→

3-amino-5-fluoro-3′,6′-dihydro-2′H-[2,4]bipyridinyl-1′-carboxylic acid tert-butyl ester

Ausbeute 65.7%

Lösungsmittel

dioxane

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturat reflux for 1 hour
2. 2
   Sonstigethe solvent evaporated in vacuo
3. 3
   workup.ADDITIONThe residue was diluted with ethyl acetate
4. 4
   Waschenwashed with water
5. 5
   Trocknenbrine, dried over sodium sulfate
6. 6
   Einengenconcentrated in vacuo

Vorschrift

A degassed solution of 2-chloro-5-fluoro-3-amino-pyridine (3.5 g), 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (8.89 g) (prepared as described in WO 2006/003494) and bis(triphenylphosphine)palladium(II) chloride (0.84 g) in dioxane (157 ml) was treated with a degassed solution of sodium carbonate (7.6 g) in water (72 ml). The reaction mixture was stirred at reflux for 1 hour, cooled to ambient temperature and the solvent evaporated in vacuo. The residue was diluted with ethyl acetate, washed with water then brine, dried over sodium sulfate and concentrated in vacuo. Chromatography on silica gel (eluent: cyclohexane/ethyl acetate 8:2) afforded 3-amino-5-fluoro-3′,6′-dihydro-2′H-[2,4]bipyridinyl-1′-carboxylic acid tert-butyl ester (4.6 g) as a solid. MS (ES+) 294 (MH+), 238 (M-isoprene); 1H NMR (400 MHz, CDCl3) 1.48 (s, 9H), 2.53 (m, 2H), 3.64 (t, 2H), 3.99 (m, 2H), 4.08 (m, 2H), 5.99 (m, 1H), 6.70 (dd, 1H), 7.85 (d, 1H).

Quelle