Water → 1-Benzyl-4-((methylamino)methyl)piperidin-4-ol
Reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[CH2:7]([N:14]1[CH2:24][CH2:23][C:17]2([O:21][C:20](=O)[NH:19][CH2:18]2)[CH2:16][CH2:15]1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.O.[OH-].[Na+]>O1CCCC1>[CH2:7]([N:14]1[CH2:24][CH2:23][C:17]([OH:21])([CH2:18][NH:19][CH3:20])[CH2:16][CH2:15]1)[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1Participants
Procedure
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°.
Workup
- temperatureThe mixture is heated
- temperatureat reflux for two hours
- filtrationThe mixture is filtered
- washthe filter cake is washed with three 200 ml portions of dichloromethane
- customEvaporation of the combined filtrates
Sources & evidence
- ORD record
- ord-7f262f37a37242ab8b16cc103be21db3
- Source dataset
- uspto-grants-1981_01
- Patent number
- US04244961
Reaction notes
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