Diisopropylethylamine → 2-methoxy-N-[phenyl-(3-pyrrolidin-1-yl-oxetan-3-yl)-methyl]-4,6-bis-trifluoromethyl-benzamide

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Reaction Steps

2,4-Bis(trifluoromethyl)-6-methoxybenzoic acid (155 mg, 0.538 mmol) was dissolved in 2 mL dimethylformamide. N,N-Diisopropyl ethyl amine (78 mg, 0.605 mmol) and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (205 mg, 0.539 mmol) were added. After 5 minutes of stirring at room temperature C-phenyl-C-(3-pyrrolidin-1-yl-oxetan-3-yl)-methylamine (intermediate B) (125 mg, 0.539 mmol) in 2 mL dimethylformamide was added. The reaction mixture was stirred at room temperature overnight. The solvent was evaporated off. The residue was taken up in 2N sodium carbonate solution and ethyl acetate and was extracted three times with ethyl acetate. The combined organic phases were dried on sodium sulfate, filtered and evaporated. Purification of the residue by flash chromatography on silica gel (heptane/ethyl acetate 1:0-1:1) yielded 2-methoxy-N-[phenyl-(3-pyrrolidin-1-yl-oxetan-3-yl)-methyl]-4,6-bis-trifluoromethyl-benzamide as an off-white solid (173 mg, 64%), MS: m/e=503.2 [(M+H)+].

Provenance & Evidence