Diisopropylamine → (2S,3R)-1-Acetoxy-2-(2,4-difluorophenyl)-3-(pyrimidin-4-yl)butan-2-ol

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Reaction Steps

A solution of diisopropylamine (30.3 g) in dry tetrahydrofuran (400 ml) was treated successively with n-butyllithium (188 ml of a 1.6M solution in hexane) followed by 4-ethylpyrimidine (32.4 g) according to the method of Example 3. A solution of the product of part (i) (64.0 g) in dry tetrahydrofuran (400 ml) was added with stirring over 0.58 hour at -40° to -50°. Acetic acid (30 ml) was then added and the solution was allowed to reach room temperature. Ether (1000 ml) and water (1000 ml) were added and the mixture was shaken. The organic layer was separated, washed with brine and dried (MgSO4). The solvent was evaporated and the residue was chromatographed on silica gel. Elution with ether/hexane (1:4) gave starting ketone initially. Further elution with ether/hexane (1:1), gradually decreasing the proportion of hexane until neat ether was being used, gave a semi-solid consisting of a (±)-enantiomeric mixture of the title compounds together with the (2R,3R)- and (2S,3S)-diastereoisomeric pair of enantiomers. Ether was added until a clear solution was obtained and then hexane (20% by volume) was added. The mixture was cooled and the resulting solid was filtered off, washed with hexane and dried to give the (±)-enantiomeric mixture of the title compounds, (23.3 g), m.p. 102°-103.5°.

Provenance & Evidence