Lithium Hydroxide → (R)-2-Acetylamino-3-methoxy-propionic acid

HRID 1852046Notes

Reaction equation

HRID 1852046 reaction equation
[CH3:1][C:2]([NH:4][C@@H:5]([C:9](NCC1C=CC=CC=1)=[O:10])[CH2:6][O:7][CH3:8])=[O:3].C[O:20]C(=O)[C@@H](CO)N.C(OP(OCC)(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)C.C(OC(=O)C)(=O)C.CN(C1C=CC=CN=1)C.[OH-].[Li+]>CO.C(N(CC)CC)C>[C:2]([NH:4][C@H:5]([CH2:6][O:7][CH3:8])[C:9]([OH:10])=[O:20])(=[O:3])[CH3:1]

Participants

9

Reactant 6

HCID 3939Lithium HydroxideHCID 7918Acetic AnhydrideHCID 218852-DimethylaminopyridineHCID 90387Methyl D-serinateHCID 159016Phosphorane, diethoxytriphenyl-, (TB-5-11)-HCID 219078Lacosamide

Product 1

HCID 10558933(R)-2-Acetylamino-3-methoxy-propionic acid

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8471TriethylamineSolvent

Procedure

Another method for the preparation of Lacosamide of Formula-I was described in the Journal Bioorganic & Medicinal Chemistry, 16(19), 8968-8975 (2008), wherein D-serine methyl ester is treated with diethoxytriphenylphosphorane to give 9:1 mixture of (R)-aziridine-2-carboxylic acid methyl and ethyl ester of Formula-XIV. The mixture of compound of Formula-XIV on acetylation with acetic anhydride in the presence of triethylamine and dimethylaminopyridine gives a mixture of (R)-1-acetylaziridine-2-carboxylic acid methyl and ethyl ester of Formula-XV. The mixture of compound of Formula-XV is treated with methanol in the presence of borontrifluoride etherate BF3.Et2O to give a mixture of (2R)-2-acetamido-3-methoxypropanic acid methyl and ethyl ester of Formula-XVI. The compound of Formula-XVI on hydrolysis with lithium hydroxide yields the compound (2R)-2-acetamido-3-methoxypropanoic acid of Formula- XVII; which on reaction with benzylamine in presence of tetrahydrofuran and 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride followed by purification of the product using flash column chromatography (10:90 MeOH/CHCl3) yields compound Lacosamide of Formula-I. The reaction sequence is as given in Scheme-4;

Workup

  1. customto give
  2. customgives
  3. additionThe mixture of compound of Formula-XV
  4. customto give

Sources & evidence

ORD record
ord-7ad5dfaf61654d589ce28c5608890275
Source dataset
uspto-grants-2015_02
Patent number
US08957252B2

Reaction notes

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