Ammonium Chloride → methyl 5-(((5aR,6S)-1-(4-fluorophenyl)-5a-methyl-5,5a,6,7,8,9-hexahydroimidazo[1,5-b]isoquinolin-6-yl)(hydroxy)methyl)thiophene-2-carboxylate

Participants

Reaction Steps

To a stirred solution of the above methyl 5-iodothiophene-2-carboxylate (175 mg, 0.65 mmol) in anhydrous THF (2 mL) cooled in an acetonitrile-dry ice bath was added isopropylmagnesium chloride solution (2 M in THF, 0.32 mL, 0.64 mmol) dropwise under nitrogen. The reaction mixture was stirred at the same temperature for 40 min before (5aR,6S)-1-(4-fluorophenyl)-5a-methyl-5,5a,6,7,8,9-hexahydroimidazo[1,5-b]isoquinoline-6-carbaldehyde (Example 1g, 100 mg, 0.32 mmol) was added. After the reaction mixture was stirred at the same temperature for 1 hr, saturated aqueous ammonium chloride solution (3 mL) was added. The mixture was extracted with ethyl acetate (3×2 mL). The combined organic solutions were dried (Na2SO4) and concentrated. Silica gel flash chromatography (50-100% ethyl acetate in heptanes then 0-20% methanol in ethyl acetate) gave methyl 5-(((5aR,6S)-1-(4-fluorophenyl)-5a-methyl-5,5a,6,7,8,9-hexahydroimidazo[1,5-b]isoquinolin-6-yl)(hydroxy)methyl)thiophene-2-carboxylate as a solid.

Provenance & Evidence