Sodium hydride → (R)-2-fluoro-5,11-dihydro-5-[1-(4-dimethylaminophenethyl)pyrrolidin-3-yl]dibenzo-[b,e][1,4]oxazepine

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Reaction Steps

60% sodium hydride (100 mg, 2.5 mmol) was washed with hexane in argon stream and then suspended in dimethyl sulfoxide (8 ml), and the obtained suspension was stirred at room temperature for 30 minutes. 2-Fluoro-5,11-dihydrodibenzo[b,e][1,4]oxazepine (538 mg, 2.5 mmol) was added to the suspension, and they were stirred at room temperature for 30 minutes and then at 50° C. for additional 40 minutes. A solution of (S)-1-(4-dimethylaminophenethyl)-3-methanesulfonyloxypyrrolidine (312 mg, 1.0 mmol, prepared by a method disclosed in International Patent No. 0040570A1) in dimethyl sulfoxide (3 ml) was added dropwise to the obtained solution, and they were stirred at 50° C. for 13 hours. The reaction mixture was poured into ice/water and then subjected to the extraction with ethyl acetate. The organic layer was dried and then the solvent was evaporated under reduced pressure. The residue was subjected to the silica gel column chromatography. After the elution with hexane and ethyl acetate (3:1) and then with hexane and ethyl acetate (1:1) as the eluent, suitable fractions were collected and the solvent was evaporated under reduced pressure to obtain (R)-2-fluoro-5,11-dihydro-5-[1-(4-dimethylaminophenethyl)pyrrolidin-3-yl]dibenzo-[b,e][1,4]oxazepine in the form of a light yellow oily substance (140 mg, 32%).

Provenance & Evidence