Hexane → 5-chloro-3-ethyl-2-naphthalen-1-yl-3H-imidazole-4-carboxylic acid ethyl ester

Temperatur

-78 °C

To a solution of 4,5-dichloro-1-ethyl-2-naphthalen-1-yl-1H-imidazole (2.87 g, 9.86 mmol) in anhydrous THF (60 ml) at −78° C. under nitrogen is added a solution of n-BuLi in hexane (1.6 M, 6.78 ml, 10.84 mmol, 1.1 eq.) dropwise. The resulting mixture is stirred at −78° C. for 1 hr, followed by the addition of dimethyl carbonate (2.66 g, 29.6 mmol, 3.0 eq.). The resulting solution is stirred at −78° C. for 30 min, warmed to rt slowly, and stirred for an additional 60 min at rt. Water (30 ml) is added to quench the reaction, and THF is evaporated under reduced pressure. The residue is extracted with EtOAc (30 ml×2) and the combined organic layers are washed with water and brine, dried over sodium sulfate, and concentrated. The crude product is purified through silica gel chromatography (hexanes/EtOAc, from 20:1 to 10:1) to give 5-chloro-3-ethyl-2-naphthalen-1-yl-3H-imidazole-4-carboxylic acid ethyl ester. LCMS 315 (M+1).

1. stirringThe resulting solution is stirred at −78° C. for 30 min
2. temperaturewarmed to rt slowly
3. stirringstirred for an additional 60 min at rt
4. customto quench
5. customthe reaction, and THF
6. customis evaporated under reduced pressure
7. extractionThe residue is extracted with EtOAc (30 ml×2)
8. washthe combined organic layers are washed with water and brine
9. dry with materialdried over sodium sulfate
10. concentrationconcentrated
11. customThe crude product is purified through silica gel chromatography (hexanes/EtOAc, from 20:1 to 10:1)

ORD-Eintrag

ord-712d0ca79ca34dd384a9ac7acc37c7c0

Quelldatensatz

uspto-grants-2010_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07728009B1