Reacción #801787

Ecuación de reacción

2-(4-bromophenoxy)tetrahydro-2H-pyran

6-Methoxy-2-(4-((S)-2-((R)-3-methylpyrrolidin-1-yl)propoxy)phenyl)chroman-4-one

tri-tert-butylphosphonium tetrafluoroborate

potassium bicarbonate

→

6-methoxy-2-(4-((S)-2-((R)-3-methylpyrrolidin-1-yl)propoxy)phenyl)-3-(4-((tetrahydro-2H-pyran-2-yl)oxy)phenyl)chroman-4-one

Disolventes

brine

ethyl acetate

1,4-dioxane water

Condiciones de reacción

Tratamiento posterior

1. 1
   Otrodegassed twice
2. 2
   Otrothe reaction mixture was degassed twice
3. 3
   TemperaturaAfter cooling
4. 4
   Otrothe two layers were separated
5. 5
   LavadoThe organic layer was washed with brine
6. 6
   Secadodried over Na2SO4
7. 7
   Filtraciónfiltered
8. 8
   Concentraciónconcentrated under reduced pressure
9. 9
   OtroThe crude material was purified
10. 10
    Otroby purified by silica gel chromatography

Procedimiento

6-Methoxy-2-(4-((S)-2-((R)-3-methylpyrrolidin-1-yl)propoxy)phenyl)chroman-4-one (420 mg, 1.06 mmol) was dissolved in 1,4-dioxane/water (4:1, 10 mL) and degassed twice. Pd2(dba)3 (11 mg, 0.011 mmol), tri-tert-butylphosphonium tetrafluoroborate (14 mg, 0.05 mmol), and potassium bicarbonate (85 mg, 0.8 mmol) were added and the reaction mixture was degassed twice. 2-(4-bromophenoxy)tetrahydro-2H-pyran (355 mg, 1.38 mmol) was then added and the reaction mixture was heated to 110° C. for 7 h. After cooling, ethyl acetate and brine were added to the reaction mixture and the two layers were separated. The organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude material was purified by purified by silica gel chromatography to afford 6-methoxy-2-(4-((S)-2-((R)-3-methylpyrrolidin-1-yl)propoxy)phenyl)-3-(4-((tetrahydro-2H-pyran-2-yl)oxy)phenyl)chroman-4-one. LCMS: 572.1 (M+H)+.

Fuente