Reacción #8730

Ecuación de reacción

2-fluoro-4-nitrobenzotrifluoride

(R)-1-methyl-pyrrolidin-3-ol

sodium hydride

→

oil

Rendimiento 46.0%

2-((R)-1-Methyl-pyrrolidin-3-yloxy)-4-nitrobenzotrifluoride

Rendimiento 46.0%

Disolventes

MeOH EtOAc

tetrahydrofuran

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroWithout removing the ice bath
2. 2
   Otroto come to room temperature
3. 3
   OtroQuenched with water (50 ml) and brine (100 ml)
4. 4
   Extracciónthen extracted into diethyl ether (5×100 ml)
5. 5
   SecadoExtracts dried over anhydrous magnesium sulfate
6. 6
   Otrofor 1 hr
7. 7
   FiltraciónFiltered through Celite
8. 8
   workup.ADDITIONThe filtrate was treated with silica (35 g)
9. 9
   Otrothen evaporated
10. 10
    Otroto give the crude product

Procedimiento

A solution of 2-fluoro-4-nitrobenzotrifluoride (12.4 g, 59.3 mmol, 1.0 eq) and (R)-1-methyl-pyrrolidin-3-ol (6.0 g, 59.3 mmol, 1.0 eq) in anhydrous tetrahydrofuran (150 ml) was cooled to 0° C. then slowly treated with portions of 60% sodium hydride (4.7 g, 0.12 mol, 2 eq) over 5 min. Without removing the ice bath, the reaction was allowed to come to room temperature and stir for 48 hrs. Quenched with water (50 ml) and brine (100 ml) then extracted into diethyl ether (5×100 ml). Extracts dried over anhydrous magnesium sulfate and decolorizing charcoal for 1 hr. Filtered through Celite. The filtrate was treated with silica (35 g) then evaporated to give the crude product suspended on silica. Column chromatography on silica (1% MeOH/EtOAc→5% MeOH/EtOAc) gave the product (Rf≡0.3 in 1% MeOH/EtOAc) as an orange oil (7.85 g, 46%).

Fuente