Phenol → Tert-butyl 4-{[2,6-dichloro-4-(phenylmethoxy)phenoxy]methyl}piperidinecarboxylate

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Reaction Steps

As depicted in Scheme 1, an appropriately substituted hydroxy compound, for example, the commercially available tert-butyl 4-(hydroxymethyl)piperidinecarboxylate was coupled with a phenol (A), for example the known compound 2,6-dichloro-4-(phenylmethoxy)phenol, affording the corresponding tert-butyl 4-{[2,6-dichloro-4-(phenylmethoxy)phenoxy]methyl}piperidinecarboxylate (A1). The intermediate (A1) was in turn treated with hydrogen gas under catalytic conditions using, for example, a Parr hydrogenation apparatus, to convert the phenylmethoxy moiety of (A1) to a hydroxy moiety, thereby making the hydroxy moiety available for further reaction. The so-prepared hydroxy derivative (A2) was then reacted with an appropriate haloalkane, for example, 1,1,1,3-tetrachloropropane, under basic conditions, yielding the corresponding dihaloalkene derivative, a compound of formula I, for example, tert-butyl 4-{[4-(3,3-dichloroprop-2-enyloxy)-2,6-dichlorophenoxy]methyl}piperidinecarboxylate. Example 1, set forth below, provides detailed methods to how compounds of formula I shown in Scheme 1 were prepared.

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