Tributyltin carboxylates with sodium chloride

Reaction of Tributyltin Carboxylates with Sodium Chloride... 

Tributyltin carboxylates act like weak acids, and can be titrated in hexane-ethanol (1 1) medium against alkali. Tributyltin chloride (TBTC1) is also a weak acid, and gives a sharp end point when similarly titrated against sodium hydroxide. TBTCl gives an instantaneous precipitate with silver nitrate in aqueous alcoholic medium. 

The presence of the propionamide fragment in the stmcture of the anti-inflammatory agent broperamole (125-1) is reminiscent of the heterocycle-based NSAID propionic acids. The activity of this agent may trace back to the acid that would result on hydrolysis of the amide. Tetrazoles are virtually always prepared by reaction of a nitrile with hydrazoic acid or, more commonly, sodium azide in the presence of acid in a reaction very analogous to a 1,3-dipolar cycloaddition. A more recent (and safer) version of the reaction noted later (see losartan, 77-4) uses tributyltin azide. In the case at hand, reaction of the anion of mefa-bromobenzonitrile (125-1) with sodium azide and an acid affords the tetrazole (125-2). Condensation of the anion from that intermediate with ethyl acrylate leads to the product from Michael addition saponiflcation gives the corresponding carboxylic acid (125-3). This is then converted to the acid chloride reaction with piperidine affords broperamole (125-4) [136]. 

Oxo-4//-pyrido[l,2-a]pyrimidine-7-carboxylates 500 were obtained when 7-iodo-4T/-pyrido[ 1,2-a]pyrimidines 499 reacted with carbon monoxide in the presence of bis(triphenylphosphine)palladium(II) chloride catalyst and triethylamine (Scheme 29) (94MI2). From 7-iodo derivatives 499, 7-vinyl derivatives 501 and 7-(l-ethoxyvinyl) derivatives 502 were prepared with vinyltributyltin in the presence of Pd(PPh3)4 and with (1-ethoxy-vinyl)tributyltin in the presence of bis(triphenylphosphine)palladium(II) chloride catalyst, respectively, in toluene at 80°C. 7-(l-Ethoxy vinyl)pyr-ido[l, 2-a]pyrimidin-4-ones 502 were hydrolyzed to yield 7-acetyl derivatives 503. The acetyl group of compounds 503 was reduced with sodium borohydride in the presence of cerium(III) chloride in ethanol to give 7-(1 -hydroxyethyl)pyridopyrimidin-4-ones 504. 

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