Phenolphthalein → N-[4-(trifluoromethyl)phenyl]-D-valine

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Reaction Steps

A solution of 10.01 g (55.3 mmol) of (R)-2-bromo-3-methylbutanoic acid in methanol is titrated with 1 M potassium hydroxide (~53 ml) in methanol to the phenolphthalein endpoint. The methanol is then removed under high vacuum at 35°, and the solid is kept at 35° under high vacuum for one hour. 4-Trifluoromethylaniline (23.89 g, 148.3 mmol) is added to the salt, and the mixture is heated in a pre-heated oil bath (90°) under nitrogen for 30 minutes. The mixture is then cooled and worked up immediately by partitioning between pentane/5% sodium hydroxide. The layers are separated and the pentane phase is extracted with 5% sodium hydroxide (2×). The combined aqueous phases are extracted with pentane (2×) and acidified with cold conc. hydrochloric acid. The aqueous phase is then extracted with ether (3×), and the combined ether phases are washed with brine and dried over magnesium sulfate. Filtration and evaporation yield (R)-2-(4-trifluoromethylphenylamino)-3-methylbutanoic acid.

Provenance & Evidence