Reaktion #1016348

Reaktionsgleichung

5-(4-bromophenyl)-2-(((3R,3aR,6R,6aS)-6-((tert-butyldimethylsilyl)oxy)hexahydrofuro[3,2-b]furan-3-yl)oxy)-6-chloro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazo[4,5-b]pyridine

tert-butyl 4-ethynylpiperidine-1-carboxylate

→

desired product

tert-butyl 4-((4-(2-(((3R,3aR,6R,6aS)-6-((tert-butyldimethylsilyl)oxy)-hexahydrofuro[3,2-b]furan-3-yl)oxy)-6-chloro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazo[4,5-b]pyridin-5-yl)phenyl)ethynyl)piperidine-1-carboxylate

Lösungsmittel

triethylamine

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeTo a round bottom flask fitted with a reflux condenser under a nitrogen atmosphere
2. 2
   TemperaturThe reaction mixture was cooled to −78°
3. 3
   Sonstigeevacuated
4. 4
   Temperaturheated to 50° C. for 17 h
5. 5
   Temperaturto cool to room temperature
6. 6
   Filtrationfiltered through Celite™
7. 7
   Waschenrinsed with ethyl acetate until the filtrate
8. 8
   EinengenThe filtrate was concentrated under reduced pressure

Vorschrift

To a round bottom flask fitted with a reflux condenser under a nitrogen atmosphere was added 5-(4-bromophenyl)-2-(((3R,3aR,6R,6aS)-6-((tert-butyldimethylsilyl)oxy)hexahydrofuro[3,2-b]furan-3-yl)oxy)-6-chloro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazo[4,5-b]pyridine (436 mg, 0.625 mmol), tert-butyl 4-ethynylpiperidine-1-carboxylate (157 mg, 0.750 mmol), CuI (9.5 mg, 0.049 mmol), and Pd(PPh3)2Cl2 (70 mg, 0.100 mmol). Then triethylamine (4.0 mL) was added. The reaction mixture was cooled to −78°, evacuated and placed under an inert nitrogen atmosphere. Then the mixture was warmed to room temperature, and heated to 50° C. for 17 h. The mixture was allowed to cool to room temperature, and then filtered through Celite™ and rinsed with ethyl acetate until the filtrate was colorless. The filtrate was concentrated under reduced pressure. Flash silica gel chromatography of the resulting residue utilizing a Biotage™ 50 G SNAP cartridge and employing a linear gradient: 0-30% EtOAc in 1:1 Hexane/DCM over 20 column volumes afforded the desired product as a clear, colorless oil following concentration under reduced pressure. LC-MS: calculated for C42H61ClN4O7Si2 824.38, observed m/e: 825.60 (M+H)+ (Rt 3.32/4 min)

Quelle