Chloroform → N-Methylbis(trifluoroacetyl)imide

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Reaction Steps

The compound of formula III is initially protected by reaction with a trimethylsilating agent such as N-methyl-N-(trimethylsilyl)trifluoroacetamide (MSTFA) in an inert solvent such as chloroform or methylene chloride. The resulting trimethylsilyl ester, in which all potentially reactive sites, such as amino, hydroxy, and carboxylic acid functions, are protected by trimethylsilyl groups, is then subjected to a reaction with iodotrimethylsilane at about 0° C. to room temperature, over a period of about twenty minutes to about two hours. The reaction mixture is then concentrated to dryness under reduced pressure, and the residue is dissolved in a suitable non-hydroxylic solvent such as acetonitrile. A small amount of tetrahydrofuran (THF) is introduced to decompose any residual traces of iodotrimethylsilane. The resulting protected iodo intermediate is then further reacted in situ with a protected form of the pipefarine derivative IV which is obtained from IV by treatment with a trimethylsilating agent such as MBTFA in a compatible solvent such as acetonitrile. The quaternization reaction is conducted at about room temperature over a period of about 30 minutes to 24 hours, preferably about 2 hours. Addition of a hydroxylic solvent such as methanol, with ice-cooling, then causes solvolysis of the trimethylsilyl protecting groups, and the quaternary iodide of formula IA precipitates. Further treatment under aqueous conditions with a base such as sodium bicarbonate or sodium hydroxide, or with sodium phosphate buffer, converts IA to the zwitterionic form I in which, depending upon the amount of base added, or the pH of the buffer, other acidic functions in the R3 and Q substituents can be converted to salts. ##STR29##

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