Development of a manufacturing process for (S)-3-(aminomethyl)-5-methylhexanoic acid, an anticonvulsant, is described. Initial preparation employed an Evans chiral alkylation on (4R,5S)-4-methyl-3-(1-oxo-4-methylpentyl)-5-phenyl-2-oxazolidinone, using benzyl bromoacetate. Use of tert-butyl bromoacetate proved advantageous for large-scale preparation. Route selection for a low-cost manufacturing process was based on "ideal process" cost projections. Four routes were evaluated in the laboratory. Of the four, two were scaled up in the pilot plant, resulting in selection of a route based on synthesis of racemic 3-(aminomethyl)-5-methylhexanoic acid, followed by resolution with (S)-(+)-mandelic acid.

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1997aminocarboxylic acids aminocarboxylic acids (hydrazinocarboxylic acids) and esters (acyclic compounds) P 0270 -091Chemical Development of CI-1008, an Enantiomerically Pure Anticonvulsant.-A large-scale low-cost process to the title compound (S)-(VI) is reported via (S)-(+)-mandelic acid-mediated resolution of (±)-(VI). -(HOEKSTRA, M. S.; SOBIERAY, D. M.; SCHWINDT, M. A.; MULH-ERN, T. A.; GROTE, T. M.; HUCKABEE, B. K.; HENDRICKSON, V. S.; FRANKLIN, L. C.; GRANGER, E. J.; KARRICK, G. L.; Org. Process Res.

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