I tried to find a way to synthesize Dimetinden (N,N-dimethyl-2-[3-(1-phenylethyl)-1⁠H-inden-2-yl]ethan-1-amine) with an Indensynthesis


First of all I would like to know if there is anything wrong with the whole synthesis and how about the yield?

Second question would be the mechanism of the inden synthesis, because it looks kind of wrong.

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    $\begingroup$ Are you asking if the linked literature procedure is correct? $\endgroup$ – NotEvans. Jun 8 '17 at 22:24
  • $\begingroup$ I am asking if my mechanism for the linked procedure makes sense and are the other parts of the synthesis possible. $\endgroup$ – Hubert Descher Jun 9 '17 at 8:47

A couple of things, first, inden-1-ol tends to tautomerize into the corresponding 1,3-dicarbonyl. Second, when adding TsCl to an alcohol, the group formed is -OTs not -OTMS, the latter is a silyl ether. The reaction with addition of TsCl requires a base such as pyridine, and because of the presence of a 1,3-dicarbonyl, rather than being added to the alcohol, it will be added to the carbon alpha to both the carbonyls. Third, the reaction of Grignard reagent should be avoided due to loss of yield because of interaction with the carbonyl. Fourth, the inden-1-ol formation is done in the presence of a base (to form enolates) which is then followed by an acid wash(to form enols which tautomerize to ketones), your mechanism seems okay if enolization occurs instead of tautomerization. Finally, the correct structure of Dimetindene is below:


I will briefly explain how I would do it from the indenol you described. First, would be a Wittig reaction using 1-(pyridin-2-yl)ethylenetriphenylphosphorane, (which can be prepared from 2-acetylpyridine) and the indenol tautomer. This will yield a beta-gamma unsaturated ketone. This product can undergo a photochemically induced [1,3] hydride shift to form an alpha-beta unsaturated ketone. This can be subject to Wolff-Kishner conditions to form Dimetindene.


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