反应详情

To a stirred mixture of 7 g lithium aluminum hydride and 150 ml tetrahydrofuran under argon is added dropwise over 20 minutes a solution of 24.6 g 8-benzyl-1-oxa-3,8-diazaspiro[4.5]decan-2-one in 150 ml tetrahydrofuran. The mixture is heated at reflux for two hours. The stirred mixture is treated with sequential dropwise addition of 7 ml water, 7 ml 15% sodium hydroxide, and 21 ml water. The mixture is filtered and the filter cake is washed with three 200 ml portions of dichloromethane. Evaporation of the combined filtrates affords 23 g of 1-benzyl-4-hydroxy-4-methylaminomethylpiperidine, an oil. A solution of 23 g 1-benzyl-4-hydroxy-4-methylaminomethylpiperidine and 250 ml dichloromethane is mixed with 100 ml of a 15% solution of phosgene in toluene. Evaporation of solvent gives a residue which is treated with 300 ml dichloromethane and 300 ml aqueous sodium bicarbonate. Separation of the dichloromethane layer followed by evaporation gives 20 g 3-methyl-3-benzyl-1-oxa-3,8-diazaspiro[4.5]decan-2-one, mp 137°-138°.

1. temperatureThe mixture is heated
2. temperatureat reflux for two hours
3. filtrationThe mixture is filtered
4. washthe filter cake is washed with three 200 ml portions of dichloromethane
5. customEvaporation of the combined filtrates