反应详情

To the solution of 3.0 g (7.16 mmol) (−)-[2-(4-chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-cyclohexyl-acetic acid methyl ester in 50 ml tetrahydrofuran were added dropwise 8.36 ml (25.1 mmol) methyl magnesiumbromide (3M in diethyl ether, commercially available) during 5 min. at room temperature. After 18 h the reaction mixture was poured onto 300 ml aqueous saturated potassium sodium tartrate solution and the phases were separated. The aqueous phase was extracted three times with ethyl acetate and the combined organic layers were washed with water and brine, dried over magnesium sulfate, filtered and evaporated to dryness. The red oil was taken up in tert-butyl methyl ether and stored in the fridge for 1 h. The precipitated solid was filtered off and washed with tert-butyl methyl ether to give a first batch of the desired compound as a slight red solid (49%). The mother liquor was purified by silica gel chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of heptane:tert-butyl methyl ether (100:0 to 50:50) to give a second batch of compound. Colorless solid (40%). MS (Turbo Spray): m/z=419.3 [M+H[ ].

1. customthe phases were separated
2. extractionThe aqueous phase was extracted three times with ethyl acetate
3. washthe combined organic layers were washed with water and brine
4. dry with materialdried over magnesium sulfate
5. filtrationfiltered
6. customevaporated to dryness
7. waitstored in the fridge for 1 h
8. filtrationThe precipitated solid was filtered off
9. washwashed with tert-butyl methyl ether