Reaktion #2254375

Reaktionsgleichung

2,5-dichloro-3-aminopyridine

1-(t-butoxycarbonyl)-4-iodo-piperidine

trimethylchlorosilane

1,2-dibromoethane

→

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

Ausbeute 46.7%

Lösungsmittel

dimethylacetamide

water

dimethylacetamide

dimethylacetamide

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONwas added dropwise (
2. 2
   workup.STIRRINGThe resulting mixture was stirred at room temperature for 30 min
3. 3
   workup.STIRRINGThe resulting mixture was stirred at 80° C. for 3 hours
4. 4
   Temperaturcooled to room temperature
5. 5
   Extraktionextracted with ethyl acetate
6. 6
   Trocknendried over sodium sulfate
7. 7
   Einengenconcentrated in vacuo

Vorschrift

A mixture of trimethylchlorosilane and 1,2-dibromoethane (7:5 v/v, 0.125 ml) was added dropwise (keeping the T° C. below 50° C.) to a suspension of zinc powder (422 mg) in dimethylacetamide (3 ml). The mixture was stirred 20 min at room temperature then a solution of 1-(t-butoxycarbonyl)-4-iodo-piperidine (1.62 g, prepared in 2 steps from 1-(t-butoxycarbonyl)-piperidin-4-one according to J. Org. Chem. 2004, 5120) in dimethylacetamide (3 ml) was added dropwise over 5 min (slightly exothermic). The resulting mixture was stirred at room temperature for 30 min then cannulated into a mixture of 2,5-dichloro-3-aminopyridine (603 mg), copper(I) iodide (42 mg) and PdCl2(dppf) (91 mg) in dimethylacetamide (5 ml). The resulting mixture was stirred at 80° C. for 3 hours, cooled to room temperature, poured into water, extracted with ethyl acetate, dried over sodium sulfate and concentrated in vacuo. The residue was subjected to silica gel chromatography (ethyl acetate:cyclohexane 3:7) to afford 3-amino-5-chloro-3′,6′-dihydro-2′H-[2,4′]bipyridinyl-1′-carboxylic acid tert-butyl ester (535 mg) as a yellow solid. 1H NMR (400 MHz, CDCl3) 1.4 (s, 9H), 1.8 (m, 4H), 2.6 (m, 1H), 2.8 (m, 2H), 3.7 (br s, 2H), 4.2 (m, 2H), 6.9 (s, 1H), 7.9 (s, 1H).

Quelle