Chlorotrimethylsilane → ethyl N-trimethylsilylpiperidin-4-ylcarboxylate

Participants

Reaction Steps

In an alternative method, ethyl piperidin-4-ylcarboxylate was reacted with trimethylsilyl chloride, yielding ethyl N-trimethylsilylpiperidin-4-ylcarboxylate (B). Intermediate (B) was then reacted with a two to three molar excess of the Grignard reagent of an appropriately substituted halide, as described above, affording a 4-[bis(substituted)hydroxymethyl]piperidine (C), for example 4-[bis(4-trifluoromethylphenyl)hydroxymethyl]piperidine. Intermediate (C) was reacted with an appropriately substituted phenylalkyl halide, as described above, yielding the corresponding intermediate N-(substituted alkyl)-4-[bis(substituted)hydroxymethyl]piperidine (I). The N-oxide of (I) and the targeted salts and betaines were prepared as describes above.

Provenance & Evidence