Hydrochloric Acid → (S)-3-[2-(4-Fluoro-phenyl)-ethyl]-3-hydroxy-4-methyl-pentanoic Acid

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Reaction Steps

The mother liquors from the isolation of the G-11 (R) enantiomer were combined, treated with 1N HCl and extracted with EtOAc. The organic phase was washed with brine, dried (MgSO4), filtered and concentrated to liberate the free β-hydroxy acid. HPLC analysis indicated the isolated material was 79% (S):21% (R). β-Hydroxy acid G-11 (22.6 g, 89.0 mmol) was dissolved in 250 mL EtOAc and treated with (R)-α-methylbenzylamine (9.17 g, 75.64 mmol). The resulting mixture was placed on a steam bath, heated to reflux, diluted with additional ˜100 mL EtOAc, and treated with hot isopropanol until solids completely dissolved. The solution was allowed to cool to room temperature slowly overnight and then cooled to −10 to −15° C. Cold EtOAc was added; the solids were filtered off and washed with cold EtOAc and Et2O to yield the title compound. The free acid was obtained by treating the salt with 1N HCl followed by extraction with EtOAc. The organic phased was washed with brine, dried (MgSO4), filtered and concentrated to afford the resolved β-hydroxy acid. HPLC analysis of isolated solid (as the free acid): (AS chiralpak column, 1 mL/min., 98% Hexanes:2% IPA:+0.1% Formic acid)

Provenance & Evidence