Red-Al → HCID 86659311, compound
Reaction equation
[CH3:1][CH:2]1[C:6](=[N:7]O)[CH2:5][C:4]2([CH2:13][CH2:12][N:11]([CH3:14])[CH2:10][CH2:9]2)[O:3]1.COCCO[AlH2-]OCCOC.[Na+]>>[CH3:14][N:11]1[CH2:12][CH2:13][C:4]2([O:3][CH:2]([CH3:1])[CH:6]3[CH:5]2[NH:7]3)[CH2:9][CH2:10]1Participants
Procedure
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-Al (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-ylamine 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.
Sources & evidence
- ORD record
- ord-8ae28ae47bfb4247bb5d05fcbbf8a6c0
- Source dataset
- uspto-grants-2014_03
- Patent number
- US08673931B2
Reaction notes
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