Sodium hydride → (r)-5,11-Dihydro-5-[1-(t-butoxycarbonyl)-2-pyrrolidinylmethyl]dibenzo[b,e][1,4]oxazepine

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Reaction Conditions

Reaction Steps

60% sodium hydride (1.44 g, 36 mmol) was washed with hexane under argon atmosphere, and then suspended in dimethyl sulfoxide (100 ml). 5,11-dihydrodibenzo[b,e][1,4]oxazepine [H. L. Yale, et al. J. Med. Chem., 7, 609 (1964)] (6.0 g, 30 mmol) was added to the obtained suspension, and the resultant mixture was stirred at 50° C. for 60 minutes. A solution of (R)-N-t-butoxycarbonyl-2-pyrrolidinylmethyl tosylate (12.8 g, 36 mmol) in dimethyl sulfoxide (60 ml) was dropped therein and the obtained mixture was stirred at 50° C. for 3 hours. The reaction solution was poured into 5% aqueous potassium bisulfate solution cooled with ice/water. After the extraction with ethyl acetate, the organic layer was washed with saturated aqueous sodium bicarbonate solution and then with saturated aqueous sodium chloride solution and dried. The solvent was evaporated under reduced pressure. The residue was treated by the column chromatography. After the elusion with a mixed solvent of ethyl acetate and hexane (1:11), the solvent was evaporated under reduced pressure to obtain (R)-5,11-dihydro-5-[1-(t-butoxycarbonyl)-2-pyrrolidinylmethyl]dibenzo[b,e][1,4]oxazepine (2.57 g, 22%).

Provenance & Evidence