First asymmetric synthesis of the antiepileptic drug Lacosamide (Vimpat®) based on a hydrolytic kinetic resolution strategy

An efficient asymmetric synthesis of the new antiepileptic drug, Lacosamide is described in high enantiopurity (>98% ee), using Jacobsen’s hydrolytic kinetic resolution strategy as a key step.

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(S)-1-(Benzyloxy)-3-methoxypropan-2-olC11H16O3[α]D25=-2.0 (c 1.55, EtOH)Source of chirality: hydrolytic kinetic resolutionAbsolute configuration: (S)

(R)-((2-Azido-3-methoxypropoxy)methyl)benzeneC11H15N3O2[α]D25=+8.3 (c 2, CHCl3)Source of chirality: hydrolytic kinetic resolutionAbsolute configuration: (R)

(S)-tert-Butyl 1-hydroxy-3-methoxypropan-2-ylcarbamateC9H19NO4[α]D25=+3.8 (c 0.95, CHCl3)Source of chirality: hydrolytic kinetic resolutionAbsolute configuration: (S)

(R)-2-(tert-Butoxycarbonylamino)-3-methoxypropanoic acidC9H17NO5[α]D25=-19.2 (c 1.4, CHCl3)Source of chirality: hydrolytic kinetic resolutionAbsolute configuration: (R)

(R)-tert-Butyl 1-(benzylamino)-3-methoxy-1-oxopropan-2-ylcarbamateC16H24N2O4[α]D25=-20.5 (c 0.9, CHCl3)Source of chirality: hydrolytic kinetic resolutionAbsolute configuration: (R)

(R)-2-Acetamido-N-benzyl-3-methoxypropanamideC13H18N2O3[α]D25=+16.1 (c 1, MeOH)Source of chirality: hydrolytic kinetic resolutionAbsolute configuration: (R)