Acetic Acid → 1-(1-Boc-4-piperidyl)-4-methyl-3,1-benzoxazin-2-one

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Reaction Steps

Acetic acid (1 ml) was added dropwise to a solution of N-tert-butoxycarbonyl-4-piperidone (9.4 g), 1-(2-amino-phenyl)-ethanol (4.3 g) and sodium cyanoborohydride (10 g) in dichloromethane and the mixture stirred at room temperature overnight. The mixture was partitioned between ethyl acetate and water, the organics separated and washed with aqueous sodium hydrogencarbonate solution, water, dried, and evaporated under reduced pressure. The crude product was dissolved in tetrahydrofuran (100 ml) and N,N-diisopropylethylamine (23 ml), cooled to 0° C., then triphosgene (4.3 g) added. The mixture was warmed to room temperature and stirred overnight. The mixture was partitioned between ethyl acetate and water, the organics washed with water, dried and evaporated under reduced pressure. Purification was by chromatography eluting with 20% ethyl acetate/isohexane. Yield 1.4 g.

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