4-(Trifluoromethoxy)aniline → 8-Methyl-2-(4-trifluoromethoxy-phenyl)-2-aza-spiro[4.5]dec-7-en-1-one

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Reaction Steps

4-(Trifluoromethoxy)-aniline (0.065 mL, [CAS Reg. No. 461-82-5]) was added to a solution of 4-(2-methoxy-ethyl)-1-methyl-2-oxa-bicyclo[2.2.2]octan-3-one (64 mg, obtained in example 59, step 1) in toluene (5 mL). The mixture was stirred for 10 minutes at r.t. Then, dimethylaluminiumchloride (1M in hexane, 0.65 mL) was added dropwise over a period of 5 minutes. The reaction mixture was stirred at reflux for 3 hours. The reaction mixture was cooled, poured into ice/water and extracted two times with ethyl acetate. The combined organic layers were washed with brine, dried over Na2SO4, filtered and the solvent was evaporated. The residue was purified by flash chromatography (silica gel, gradient of heptane in ethyl acetate) to give 8-methyl-2-(4-trifluoromethoxy-phenyl)-2-aza-spiro[4.5]dec-7-en-1-one as a light yellow solid as the main product (81 mg, 77%). MS (m/e)=326.4 [MH+]. From this reaction, a small amount of (5α,8α)-8-hydroxy-8-methyl-2-(4-trifluoromethoxy-phenyl)-2-aza-spiro[4.5]decan-1-one (see example 57) was also isolated (6 mg, 5%).

Provenance & Evidence