Citric Acid → (r)-2-[2-(Tert-butoxy)-2-oxoethyl]-5-(2-methyl-1,1'-biphenyl-4-yl)-pentanoic acid (s)-alpha-methylbenzylamine salt

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Reaction Conditions

Reaction Steps

(R)-2-[2-(tert-butoxy)-2-oxoethyl]-5-(2-methyl-1,1′-biphenyl-4-yl)-pentanoic acid can be enantiomerically upgraded as the (S)-alpha-methylbenzylamine salt. Thus, (R)-2-[2-(tert-butoxy)-2-oxoethyl]-5-(2-methyl-1,1′-biphenyl-4-yl)-pentanoic acid cyclohexylamine salt (50 g, 0.10 mol, enantiomeric excess=72%) was partitioned between ethyl acetate (750 ml) and aqueous citric acid solution (10%, 750 ml). The organic phase was separated, washed with water (500 ml), then azeotropically dried by distillation at constant volume. (S)-alpha-methylbenzylamine (13.2 ml, 0.10 mol) was added dropwise over 5 min at 40° C., the mixture was allowed to cool to 20-25° C., and was then stirred for 24 hours. The mixture was filtered and the residue was washed with ethyl acetate (100 ml) and then dried in vacuo) at 45° C. for 2 hours to leave the title compound as a colourless solid (41.0 g, 91% yield, enantiomeric excess=96.4%, 95% pure by NMR).

Provenance & Evidence