Réaction #155550

Équation de réaction

[5-(trifluoromethyl)pyridin-3-yl]boronic acid

cesium carbonate

water

tert-Butyl[(4aS,5R,7aS)-7a-(5-bromo-2-fluorophenyl)-5-methyl-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-yl]imidodicarbonate

→

title compound

Rendement 25.0%

(4aS,5R,7aS)-7a-(2-Fluoro-5-(5-(trifluoromethyl)pyridine-3-yl)phenyl)-5-methyl-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-amine

Rendement 25.0%

Solvants

NaHCO3

ethanol

1,2-dimethoxyethane

Conditions de réaction

Traitement

1. 1
   Températurethe reaction mixture was cooled to room temperature
2. 2
   Extractionextracted with EtOAc (×3)
3. 3
   SéchageThe combined organic layers were dried (MgSO4)
4. 4
   Filtrationfiltered
5. 5
   Concentrationconcentrated in vacuo
6. 6
   AutreThe residue was purified
7. 7
   workup.DISSOLUTIONThe purified product was dissolved in DCM (2 mL)
8. 8
   workup.WAITAfter 1 hour
9. 9
   Autrethe solvents were removed in vacuo
10. 10
    Extractionextracted with DCM (×2)
11. 11
    SéchageThe combined organic layers were dried (MgSO4)
12. 12
    Filtrationfiltered
13. 13
    Concentrationconcentrated

Mode opératoire

tert-Butyl[(4aS,5R,7aS)-7a-(5-bromo-2-fluorophenyl)-5-methyl-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-yl]imidodicarbonate (0.15 g, 0.34 mmol) was dissolved in 1,2-dimethoxyethane (1.5 mL), water (0.7 mL) and ethanol (0.5 mL). The resulting solution was heated to 100° C. and to it was added [5-(trifluoromethyl)pyridin-3-yl]boronic acid (0.32 g, 1.68 mmol), cesium carbonate (0.659 g, 2.02 mmol) and dichloropalladium-triphenylphosphane (0.047 g, 0.067 mmol) and the reaction was stirred at 100° C. After 1 hour, the reaction mixture was cooled to room temperature, diluted with saturated aqueous NaHCO3 and extracted with EtOAc (×3). The combined organic layers were dried (MgSO4), filtered and concentrated in vacuo. The residue was purified using column chromatography (gradient 0-60% EtOAc in hexane). The purified product was dissolved in DCM (2 mL) and trifluoroacetic acid (2 L). After 1 hour, the solvents were removed in vacuo. The residue was neutralised with saturated aqueous NaHCO3 and extracted with DCM (×2). The combined organic layers were dried (MgSO4), filtered and concentrated to give the title compound (35 mg, colourless solid).

Source