Enzymatic resolution of racemic (2r,s)-2-(acetylamino)-3-methoxy-n-(phenylmethyl)propanamide
AssigneeMedichem, S.A.
InventorsJordi Bosch i Lladó, Ernesto Durán López
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Abstract
The present invention is concerned with a process of preparing (R)-lacosamide. The process comprises providing an (R,S)-lacosamide precursor and contacting the same with at least an enzyme in the presence of a solvent. The enzyme either stereoselectively hydrolyzes or acetylates an (R)- or (S)-enantiomer of the (R,S)-lacosamide precursor. The process further comprises where appropriate also concurrently, or successively, employing one or more reagents capable of converting the hydrolysed or acetylated (R)- or (S)-enantiomer to (R)-lacosamide.
Claims25
-40. (canceled)
A process of preparing (R)-lacosamide of formula (I):
- comprising:
- (i) providing an (R,S)-compound of formula (II):
- wherein
- R1 is selected from the group consisting of CH3C(═O)— and a first intermediate moiety capable of being converted into CH3C(═O)—;
- R2 is selected from the group consisting of —NHCH2Ph and a second intermediate moiety capable of being converted into —NHCH2Ph;
- (ii) contacting the (R,S)-compound of formula (II) with one or more enzymes in the presence of a solvent and optionally an acetyl donor compound to form an enantiomerically enriched or enantiomerically pure (R)-enantiomer of the compound formula (II),
- wherein the one or more enzymes is capable of stereoselectively hydrolyzing either the (R)- or (S)-enantiomer of the compound of formula (II) when the solvent comprises a protic solvent, or is capable of stereoselectively acetylating either the (R)- or (S)-enantiomer of a compound of formula (II) when R1 is a first intermediate moiety and when an acetyl donor compound is present;
- and
- (iii) optionally further comprising contacting the (R,S)-compound of formula (II) or the enantiomerically enriched or enantiomerically pure (R)-enantiomer of the compound formula (II) with one or more reagents capable of converting a first intermediate moiety into CH3C(═O)—, and/or said second intermediate moiety into —NHCH2Ph.
A process of preparing (R)-lacosamide of formula (I):
- comprising:
- (i) providing an (R,S)-compound of formula (IIa):
- wherein
- R2 is selected from the group consisting of —NHCH2Ph and an intermediate moiety capable of being converted into —NHCH2Ph;
- X is selected from the group consisting of hydrogen or a leaving group;
- (ii) contacting the (R,S)-compound of formula (IIa) with an acetyl donor compound and one or more enzymes capable of stereoselectively acetylating the (R)-enantiomer of a compound of formula (IIa) to form an enantiomerically enriched or enantiomerically pure (R)-enantiomer of the compound formula (III):
- and
- (iii) optionally further comprising contacting the (R,S)-compound of formula (IIa) or the enantiomerically enriched or enantiomerically pure (R)-enantiomer of the compound formula (III) with one or more reagents capable of converting an intermediate moiety into —NHCH2Ph.
A process of preparing (R)-lacosamide of formula (I):
- comprising:
- (i) providing an (R,S)-compound of formula (IIb):
- wherein R2 is selected from the group consisting of —NHCH2Ph and an intermediate moiety capable of being converted into —NHCH2Ph;
- (ii) contacting the (R,S)-compound of formula (III)) with one or more enzymes capable of stereoselectively hydrolyzing either the (R)- or (S)-enantiomer of the compound of formula (IIb) in the presence of a protic solvent thereby providing an enantiomerically enriched, or enantiomerically pure (R)-enantiomer of a compound of formula (III):
- (iii) optionally further comprising contacting an (R,S)-compound of formula (IIb) or the enantiomerically enriched, or enantiomerically pure (R)-enantiomer of a compound of formula (III) with one or more reagents capable of converting the intermediate moiety into —NHCH2Ph.
Dependencies are inferred from the claim text.