Reaktion #305190

Reaktionsgleichung

2-Fluoropyridine-3-boronic acid

sodium carbonate

N,N-di(tert-butyloxycarbonyl)-[(4aR,6R,8aS)-8a-(5-bromo-2-fluorophenyl)-6-fluoromethyl-4,4a,5,6,8,8a-hexahydro-7-oxa-3-thia-1-azanaphthalen-2-yl]amine

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title compound

Ausbeute 91.2%

(4aR,6R,8aS)-8a-[2-fluoro-5-(2-fluoropyridin-3-yl)phenyl]-6-fluoromethyl-4,4a,5,6,8,8a-hexahydro-7-oxa-3-thia-1-azanaphthalen-2-ylamine

Ausbeute 91.2%

Lösungsmittel

DMF

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturAfter cooling to room temperature
2. 2
   ExtraktionThe aqueous layer was extracted with ethyl acetate
3. 3
   Waschenthe organic layer was washed with water
4. 4
   TrocknenThe organic layer was dried over anhydrous magnesium sulfate
5. 5
   Sonstigethe solvent was evaporated under reduced pressure
6. 6
   SonstigeThe residue was purified by silica gel column chromatography
7. 7
   workup.DISSOLUTIONThe resulting intermediate was dissolved in dichloromethane (4.0 ml)
8. 8
   workup.ADDITIONTFA (1.0 ml) was added
9. 9
   workup.STIRRINGthe mixture was stirred at room temperature for three hours
10. 10
    workup.ADDITIONIce was added to the reaction mixture
11. 11
    ExtraktionThe aqueous layer was extracted with chloroform
12. 12
    Trocknenthe organic layer was dried over anhydrous magnesium sulfate
13. 13
    SonstigeThe solvent was evaporated under reduced pressure
14. 14
    Sonstigethe residue was purified by silica gel column chromatography

Vorschrift

2-Fluoropyridine-3-boronic acid (51.1 mg), tetrakis(triphenylphosphine)palladium (19.1 mg) and a 1 N sodium carbonate solution (363 μl ) were added to a solution of N,N-di(tert-butyloxycarbonyl)-[(4aR,6R,8aS)-8a-(5-bromo-2-fluorophenyl)-6-fluoromethyl-4,4a,5,6,8,8a-hexahydro-7-oxa-3-thia-1-azanaphthalen-2-yl]amine (95 mg) in DMF (6.79 ml). After replacement with nitrogen, the mixture was stirred at 85° C. for two hours. After cooling to room temperature, the mixture was diluted with water. The aqueous layer was extracted with ethyl acetate, and the organic layer was washed with water. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography. The resulting intermediate was dissolved in dichloromethane (4.0 ml). TFA (1.0 ml) was added and the mixture was stirred at room temperature for three hours. Ice was added to the reaction mixture, followed by neutralization with a sodium bicarbonate solution. The aqueous layer was extracted with chloroform, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography to obtain the title compound (59.0 mg).

Quelle