Hexamethylphosphoramide → tert-Butyl 2-methyl-4-oxopiperidine-1-carboxylate

참여 물질

반응 단계

A solution of 4.0 gm (20.28 mMol) 1-(tert-butoxycarbonyl)-1,2,3,4-tetrahydropyridin-4-one and 4.21 gm (20.48 mMol) copper(I) bromide-dimethylsulfide complex in 160 mL tetrahydrofuran was cooled to −780C. To this solution was added 7.43 mL (22.31 mMol) methyl magnesium chloride (3.0 M in tetrahydro-furan). After stirring for 1 hour at −78° C. an additional equivalent of methyl magnesium chloride was added and stirring continued for an additional 30 minutes. The reaction mixture was then treated with 10 mL hexamethylphosphoramide followed by the addition of a solution of 15.93 gm (40.56 mMol) 2-[N,N-bis(trifluoromethylsulfonyl)amino]-5-chloropyridine in 50 mL tetrahydrofuran. The reaction mixture was allowed to warm to room temperature and was stirred at room temperature overnight. The reaction mixture was then diluted with 1.5 L diethyl ether and was washed sequentially with 2×500 mL saturated aqueous oxalic acid, 500 mL water, 2×500 mL saturated aqueous sodium bicarbonate, and 500 mL saturated aqueous sodium chloride. The remaining organics were dried over magnesium sulfate and concentrated under reduced pressure. The residue was suspended in hexanes and then filtered. The filtrate was concentrated under reduced pressure and the residue subjected to silica gel chromatography, eluting with a gradient of hexane containing 0-50% ethyl acetate. Fractions containing product were combined and concentrated under reduced pressure to provide 1.92 gm of the title compound as an oil that gradually formed a crystalline mass.

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