Reaktion #8730

Reaktionsgleichung

2-fluoro-4-nitrobenzotrifluoride

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

sodium hydride

→

oil

Ausbeute 46.0%

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

Ausbeute 46.0%

Lösungsmittel

MeOH EtOAc

tetrahydrofuran

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeWithout removing the ice bath
2. 2
   Sonstigeto come to room temperature
3. 3
   SonstigeQuenched with water (50 ml) and brine (100 ml)
4. 4
   Extraktionthen extracted into diethyl ether (5×100 ml)
5. 5
   TrocknenExtracts dried over anhydrous magnesium sulfate
6. 6
   Sonstigefor 1 hr
7. 7
   FiltrationFiltered through Celite
8. 8
   workup.ADDITIONThe filtrate was treated with silica (35 g)
9. 9
   Sonstigethen evaporated
10. 10
    Sonstigeto give the crude product

Vorschrift

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%).

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