4-Hydroxybenzaldehyde → 4-Isobutoxybenzaldehyde

Participants

Reaction Steps

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:

Provenance & Evidence