反应详情

The precursor amine compounds may in turn be prepared as described in greater detail below. Thus, for example, 2,8-Dimethyl-1-oxa-3,8-diaza-spiro[4.5]decane may be obtained by reaction of 4-aminomethyl-1-methyl-piperidin-4-ol with acetaldehyde in dry dichloromethane. 2,8-Dimethyl-1-oxa-4,8-diazaspiro[4.5]decane may be obtained by reaction of 1-amino-2-propanol with 1-methyl-4-piperidone under reflux. 1′,4-Dimethylspiro[3-oxa-6-azabicyclo[3.1.0]hexane-2,4′-piperidine] may be obtained by first preparing 2,8-dimethyl-1-oxa-8-azaspiro[4.5]decan-3-one oxime from 1-methyl-4-piperidone via 2,8-dimethyl-1-oxa-8-azaspiro[4.5]decan-3-one per the procedure of Tsukamoto et. al., Chem. Pharm. Bull. 1995, 43, 842-852, followed by reduction of the oxime with Red-A1 (sodium bis(2-methoxyethoxy)aluminumhydride) and then basic workup to yield 1′,4-Dimethylspiro[3-oxa-6-azabicyclo[3.1.0]hexane-2,4′-piperidine]. 2,8-Dimethyl-1-oxa-8-aza-spiro[4.5]dec-3-yl amine may be obtained by first preparing 2,8-dimethyl-1-oxa-8-azaspiro[4.5]decan-3-one oxime from 1-methyl-4-piperidone via 2,8-dimethyl-1-oxa-8-azaspiro[4.5]decan-3-one per the procedure of Tsukamoto et. al., Chem. Pharm. Bull. 1995, 43, 842-852, followed by reduction of the oxime with lithium aluminum hydride/aluminum chloride. Compounds of formula I may then be prepared from these amines by an appropriate coupling reaction.