4-Hydroxybenzaldehyde → 4-Isobutoxybenzaldehyde
Reaction equation
C(N)(N)=O.[OH:5][C:6]1[CH:13]=[CH:12][C:9]([CH:10]=[O:11])=[CH:8][CH:7]=1.[CH2:14](Br)[CH:15]([CH3:17])[CH3:16].[I-].[K+].C(=O)([O-])[O-].[K+].[K+]>>[CH2:14]([O:5][C:6]1[CH:13]=[CH:12][C:9]([CH:10]=[O:11])=[CH:8][CH:7]=1)[CH:15]([CH3:17])[CH3:16]Participants
Procedure
A method of synthesizing N-(1-methylpiperidin-4-yl)-N-(4-fluorophenylmethyl)-N′-(4-(2-Another embodiment disclosed herein includes a) phenylmethyl)carbamide, including reacting the 4-hydroxybenzaldehyde with isobutylbromide in the presence of potassium iodide and potassium carbonate to produce 4-isobutoxybenzaldehyde, reacting the 4-isobutoxybenzaldehyde with about 1.5 equivalents of NH2OH to produce 4-isobutoxybenzoxime, reacting the 4-isobutoxybenxoxime with H2 in the presence of Raney-Ni and from about 13 to about 16 equivalents of NH3 to produce (4-isobutoxyphenyl)methanamino acetate, reacting the (4-isobutoxyphenyl)methanamino acetate with about 30% NaOH and extracting with toluene to produce (4-isobutoxyphenyl)methanamine, reacting the (4-isobutoxyphenyl)methanamine with HCl and COCl2 in the presence of toluene to produce 1-isobutoxy-4-(isocyanatomethyl)benzene, and reacting the 1-isobutoxy-4-(isocyanatomethyl)benzene with N-(4-fluorobenzyl)-1-methylpiperidin-4-amine to produce N-(1-methylpiperidin-4-yl)-N-(4-fluorophenylmethyl)-N′-(4-(2-methylpropyloxy)phenylmethyl)carbamide. In one embodiment, the product of the method comprises than about 0.2% by weight of Impurity 1:
Workup
- customA method of synthesizing N-(1-methylpiperidin-4-yl)-N-(4-fluorophenylmethyl)-N′-(4-(2-Another embodiment
Sources & evidence
- ORD record
- ord-fbefa9bc805a4816ae573ce7d43c9f52
- Source dataset
- uspto-grants-2010_09
- Patent number
- US07790899B2
Reaction notes
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