Benzyl chloroformate → Z-D-Ser-OH

HRID 1852044Notes

Reaction equation

[NH2:1][C@@H:2]([C:5]([OH:7])=[O:6])[CH2:3][OH:4].[CH2:8]([O:15][C:16](Cl)=[O:17])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1>>[CH2:8]([O:15][C:16]([NH:1][C@@H:2]([C:5]([OH:7])=[O:6])[CH2:3][OH:4])=[O:17])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1

Participants

Reactant 2

HCID 10387Benzyl chloroformate

HCID 71077D-Serine

Product 1

HCID 489184Z-D-Ser-OH

Procedure

The second method describes the process, wherein D-serine is protected with benzyloxycarbonyl chloride to give N-Benzyloxycarbonyl-D-serine of Formula-IV. The compound of Formula-IV on alkylation with methyl iodide in the presence of silver oxide and solvent acetonitrile yields the compound (2R)-methyl 2-(benzyloxycarbonylamino)-3-methoxypropanoate of Formula-V, and which is purified by flash column chromatography using silica gel and methanol-chloroform eluent before the next stage. The compound of Formula-V is hydrolyzed to give (2R)-2-(benzyloxycarbonylamino)-3-methoxypropanoic acid of Formula-VI. The compound of Formula-VI is cooled to −78° C. in tetrahydrofuran and reacted with isobutyl chloroformate in presence of N-methylmorpholine followed by reaction with benzylamine to yield the compound (2R)-benzyl 1-(benzylamino)-3-methoxy-1-oxopropan-2-ylcarbamate of Formula-VII. The compound of Formula-VII on hydrogenation using palladium on carbon gives deprotected compound (2R)-2-amino-N-benzyl-3-methoxy-propanamide of Formula-VIII. The compound of Formula-VIII is acetylated using acetic anhydride in the presence of solvent pyridine to give crude Lacosamide of the Formula-I. The crude compound is purified by flash column chromatography to give pure Lacosamide.

Sources & evidence

ORD record: ord-b27bdd126ed5471ca6fda20091c60cce
Source dataset: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08957252B2

Reaction notes

Loading…