FIELD OF THE INVENTION

The present invention relates to an improved process for the preparation of Lacosamide of Formula (I).

BACKGROUND OF THE INVENTION

Lacosamide is chemically known as (R)-2-acetamido-N-benzyl-3-methoxypropionamide (I).

Lacosamide is an anticonvulsant, which selectively enhances slow inactivation of voltage-gated sodium channels, resulting in stabilization of hyperexitable neuronal membranes and inhibition of repetitive neuronal firing. Lacosamide is marketed under the trade name Vimpat®. It has been approved for the treatment of partial-onset seizures.
Lacosamide and its pharmaceutically acceptable salts are disclosed in US 5,654,301 and RE 38,551 E (US 5,773,475).

According to the process disclosed in US '551, Lacosamide of Formula (I) is prepared by reacting D-Serine (II) with methanol in the presence of HC1 to produce D-Serine methyl ester hydrochloride (III), which is reacted with benzylamine to produce (R)-N-benzyl-2-amino-3-hydroxypropionamide (IV), which is further acetylated in the presence of acetic anhydride, followed by recrystallization to produce (R)-N-benzyl-2-acetamido-3-hydroxypropionamide (V). Compound (V) is further reacted with methyl iodide in the presence of silver oxide to produce Lacosamide of Formula (I).

The process is as shown in Scheme -I below:

US '551 also discloses a variant process for the preparation of Lacosamide of Formula (I), by reacting D-Serine (II) with acetic anhydride in acetic acid to produce (R)-2-acetamido-3-hydroxypropionic acid (VI), which is further reacted with benzylamine to produce (R)-N-benzyl-2-acetamido-3-hydroxypropionamide (V), which is further reacted with methyl iodide in the presence of silver oxide to produce Lacosamide of Formula (I).

The process is as shown in Scheme -II below:

The above processes comprise the benzylamide formation prior to the O-methylation. However, this processes results in Lacosamide with various impurities, which must be removed by column chromatography. Employing column chromatography technique is tedious and laborious and also involves use of large quantities of solvents, and hence is not suitable for industrial scale operations.

US '551 also discloses another variant process for the preparation of Lacosamide of Formula (I), by reacting D-Serine with benzylchloroformate (Cbz-CI) in the presence of magnesium oxide to produce Cbz-D-Serine (VII), which is further reacted with methyl iodide in the presence of silver oxide and methyl cyanide to produce (R)-methy-2-(carbobenzyloxyamino)-3-methoxypropionate (VIII). Compound (VIII) is treated with anhydrous K2CO3 in the presence of aqueous methanol to produce (R)-2-(carbobenzyloxyamino)-3-methoxypropionic acid (IX), which is reacted with benzylamine in the presence of N-methylmorpholine and isobutyl chloroformate in dry THF to produce (R)-2-(carbobenzyloxyamino)-3-methoxypropionamide (X), which is further reacted with hydrogen gas in the presence of palladium-carbon and methanol to produce N-benzyl-2-amino-3-methoxypropionamide (XI). Acetylation of N-benzyl-2-amino-3-methoxypropionamide (XI) with acetic anhydride in the presence of pyridine in THF to produce Lacosamide of Formula (I).

The process is as shown in Scheme -III below:

US 6,048,899 discloses another variant process for the preparation of Lacosamide of Formula (I), by reacting D-Serine with benzylchloroformate (Cbz-Cl) in the presence of magnesium oxide to produce Cbz-D-Serine (VII), which is further reacted with benzylamine in the presence of N-methylmorpholine and isobutyl chloroformate to produce (R)-N-benzyl-2-(carbobenzyl-oxyamino)-3-hydroxypropionamide (Xa). which is reacted with methyl iodide in the presence of silver oxide to produce (R)-N-benzyl-2-(carbobenzyloxyamino)-3-methoxypropionamide (X). Compound (X) which is hydrogenated in the presence of palladium catalyst to produce N-benzyl-2-amino-3-methoxypropionamide (XI). Acetylation of N-benzyl-2-amino-3-methoxy-propionamide (XI) with acetic anhydride in the presence of pyridine in THF to produce Lacosamide of Formula (I).

The process is as shown in Scheme -IV below:

The disadvantage with the above processes is the use of silver oxide in the O-methylation step. This reagent is highly expensive and results in partial racemisation, which reduces the yield.

Further, removal of the S-enantiomer of Lacosamide is more difficult at this stage, which requires repeated crystallizations. Additionally, a second and third crystallization reduces yield as some Lacosamide of Formula (I) remains uncrystallized and is not recovered from the liquid phase.

US 2008/0027137 Al discloses a process for the preparation of Lacosamide of Formula (I), by methylation of N-Boc-D-serine (XII) with dimethyl sulphate and butyllithium or dimethyl sulphate in the presence of a base and phase transfer catalyst (PTC) to produce (R)-N-Boc-amino-3-methoxy-propanoic acid (XIII), which is further reacted with benzylamine in the presence of isobutyl chloroformate and N-methylmorpholine to produce (R)-N-benzyl-2-Boc-amino-3-methoxy- propionamide (XIV). Compound (XIV) is converted to (R)-N-benzyl-2-amino-3-methoxypropionamide (XI) by treating with HCI in water, which is further reacted with acetic anhydride in ethyl acetate to produce Lacosamide of Formula (I).

The process is as shown in Scheme -V below:

US 2009/0143472 discloses a process for the preparation of Lacosamide of Formula (I), by reacting N-trityl-D-serine (XV) with methyl iodide in THF to produce O-methyl-N-trityl-D-serine (XVI), which is further reacted with benzylamine in the presence of isobutyl chloroformate (IBCF) and N-methylmorpholine (NMM) to produce N-benzyl-O-methyl-N-trityl-D-serinamide (XVII). Compound (XVII) is converted to N-benzyl-2-amino-3-methoxypropionamide (XI) in the presence of HC1 in MDC. Compound (XI) is further reacted with acetic anhydride in dimethylaminopyridine to produce Lacosamide of Formula (I).

The process is as shown in Scheme -VI below:

US '472 also discloses a variant process for the preparation of Lacosamide of Formula (I), by reacting N-trityl-D-serine with benzylamine in the presence of isobutyl chloroformate and N-methylmorpholine to produce N-benzyl-N-trityl-D-serinamide (XVIII). Compound (XVIII) is reacted with methyl iodide in THF to produce N-benzyl-O-methyl-N-trityl-D-serinamide (XVII), which is further converted to N-benzyl-2-amino-3-methoxypropionamide (XI) in the presence of HC1 in MDC. Compound (XI) is further reacted with acetic anhydride in dimethylamino pyridine to produce Lacosamide of Formula (I).

The process is as shown in Scheme -VII below:

US 2009/0298947 Al discloses crystalline Form-I, Form-II and amorphous Forms of Lacosamide.

There is a need to develop cost effective and commercially viable process, which provides Lacosamide with high selectivity and without racemisation.

Further, there is a need to develop a purification process, which reduces the unwanted impurities to a pharmaceutically acceptable limit, which inturn provides Lacosamide of high purity with improved yield.

The present invention is specifically directed towards a process, wherein O-methylation of N-benzyl-N-protected-amino-3-hydroxypropionamide of formula (XX), followed by deprotection and N-acetylation to produce Lacosamide of Formula (I). The present invention provides Lacosamide with high purity and yield without racemisation.

The instant invention also directed to a purification process using specific solvents selected from water, isopropyl acetate and there mixtures thereof, which results in pure crystalline Lacosamide Form I.

OBJECTIVE OF THE INVENTION

The main objective of the present invention is to provide a simple and effective process for the preparation of Lacosamide of formula (I) with high purity and good yield on a commercial scale.

SUMMARY OF THE INVENTION

The present invention provides an improved process for the preparation Lacosamide of Formula I,

which comprises:

(i) O-methylation of a compound of Formula (XX); in the presence of a methylating agent and a base to produce Formula (XXI), with proviso that the O-methylation is not carried out in the presence of silver oxide;

(ii) deprotecting the compound of Formula (XXI) to produce a compound of Formula (XI);

(iii) acetylating the compound of Formula (XI) to produce Lacosamide of Formula (I).
Another embodiment of the present invention provides a process for the preparation of compound of formula (XX), which comprises: reacting a compound of Formula (XIX);
wherein, R represents N-protecting group; with benzylamine in the presence of a base and an activator of the carboxyl group in a solvent to produce a compound of Formula (XX);

According to an embodiment, the present invention also provides a process for the purification of Lacosamide of Formula I, comprises:

(i) preparing a solution of crude Lacosamide in a solvent selected from dichloromethane, isopropyl acetate, di-n-butyl ether, water and mixtures thereof;

(ii) optionally, filtering the solution of step (i);

(iii) precipitating Lacosamide Form I by cooling the solution;

(iv) isolating pure Lacosamide in crystalline Form I.

DETAILED DESCRIPTION OF THE INVENTION

The present invention provides an improved process for the preparation of Lacosamide of Formula I.

The process comprises, N-protected D-serine (XIX) with benzylamine in the presence of a suitable base and an activator of carboxyl group in a suitable solvent to produce compound of formula (XX). N-protecting group, of the compound of formula (XIX) is selected from t-butoxycarbonyl (Boc), carbobenzoxy (Cbz), 9-fluorenyl methyloxycarbonyl (9-FMOC),

The suitable base used in the above reaction is selected from triethylamine, diisopropylethylamine, l,8-diazabicyclo[5.4.0]undec-7-ene, 1,4-diazabicyclo-[2.2.2]octane, potassium bicarbonate, potassium carbonate, sodium carbonate, sodium bicarbonate, morpholine derivative, preferably 4-methylmorpholine and an activator of the carboxyl group is selected from carbodiimide, N,N-carbonyldiimidazole N,N-dimethylaminopyridine(DMAP) or an alkyl chloroformate, preferably isobutyl chloroformate.

The suitable organic solvents for the above reaction are selected from halogenated solvents, such as dichloromethane, ethylene dichloride, and chloroform; ether, toluene, ethyl acetate. The reaction is performed at a temperature ranging from -10°C to about 35°C based on the solvent or mixture of solvents used for the reaction. The activator of the carboxyl group and base are added to the solution of compound of Formula (XIX) in the organic solvent. More preferably, the reagent is added slowly in a drop-wise manner.
Most preferably, this addition is while maintaining the reaction mixture at a temperature of about -10°C to about 5°C. The sufficient period of time necessary for obtaining compound (XX) will depend on the parameters of the reaction. Preferably, maintaining the reaction mixture for about 1 to about 6 hours. More preferably, the reaction mixture is maintained for 1 hour to about 2 hours.

The compound (XX) obtained by the above process is used as such in the next step or isolated by precipitation of compound from the reaction mixture or by removing the solvent from the reaction mixture.

O-methylation of a compound (XX) is performed in the presence of methylating agent to produce a compound of Formula (XXI). Methylating agent is selected from methyl halide such as methyl iodide, methyl chloride, methyl bromide, methyl fluoride; dimethyl sulfate, trimethyl silyldiazomethane, dimethyl sulfoxide (DMSO). The most preferred methylating agent is dimethyl sulfate. The reaction is performed in the presence of a base, which is selected from hydride, hydroxide and/or oxides of metals such as hydride, carbonates, hydroxide and/or oxides of sodium, potassium and calcium. The most preferred base is sodium or potassium hydroxide.

The O-methylation can optionally be performed in the presence of a phase transfer catalyst (PTC), selected from tetraethylammonium-p-toluenesulfonate, tetrapropylammonium trifluoromethane sulfonate, tetraphenylphosphonium hexafluoroantimonate, acetylpyridinium bromide, triphenylmethyl triphenylphosponium chloride, benzyltriethylammonium chloride, benzyltrimethylammonium chloride, benzyltriphenylphosphonium chloride, benzytributyl-ammonium chloride, butyltriethylammonium bromide, butyltriphenylphosphonium bromide, cetyltrimethyl ammonium bromide, cetyltrimethyl ammonium chloride, ethyltriphenyl-phosphonium bromide, ethyltriphenylphosphonium iodide, methyltrioctylammonium bromide, methyltriphenylphosphonium bromide, methyltriphenylphosphonium iodide, phenyltrimethyl ammonium chloride, tetrabutylammonium hydroxide, tetrabutylammonium perchlorate, tetrabutylammonium bromide, tetrabutylammonium hydrogensulphate, tetrabutylammonium iodide, tetrabutylammonium tetrafluoroborate, tetrabutylammonium thiocyanate, tetraethylammonium hydroxide, tetraethylammonium iodide, tetraethylammonium bromide, tetramethylammonium chloride, tetramethylammonium iodide, tetramethylammonium chloride, tetraoctylammonium bromide, tetraphenylphosphonium bromide, tetrapropylammonium hydroxide, tetrapropylammonium bromide and tributylmethyl- ammonium chloride, wherein tetrabutylammonium salts and particularly tetra- butylammonium halides, e.g. the bromide are especially preferred.

The solvents that are used for the O-methylation reaction are generally organic solvents selected from tetrahydrofuran (THF), dichloromethane (MDC), dimethyl sulfoxide (DMSO), acetonitrile (MeCN), ethyl acetate, acetone, 1,2-dimethoxy ethane, monoglyme, diglyme or mixture thereof. The methylating agent is added to the mixture containing compound of formula (XX), base and an organic solvent. The reaction is usually allowed to proceed for at least 2 hours at -10 to 20°C, and preferably for 2.5-5 hours at 0 to 10°C. Also, the reaction is performed at higher or lower temperatures such as any temperature between -20 and 20°C if the reaction time is adapted accordingly. The O-methylated compound of Formula (XXI) is then isolated from the mixture and optionally purified.

Compound of Formula (XXI) is then subjected to de-protection to produce a compound of Formula (XI). The de-protection reaction is performed using de-protecting agents selected from acids. Strong as well as mild acidic conditions are suitable for the de-protection reaction. Mild acids such as acetic acid, oxalic acid, tartaric acid, phosphoric acid (H3PO4), sodium hydrogen phosphate (Na2HPO4), etc. or strong acid e.g., hydrochloric acid, sulphuric acid, trifluoroacetic acid, etc. are used. Organic solvent is selected from aromatic or aliphatic solvent. Aromatic solvents such as toluene, xylene, etc., and aliphatic solvents such as chlorinated solvents dichloromethane, chloroform; alcohols such as methanol, ethanol, isopropanol; ethyl acetate, cyclopentyl methyl ether are used in de-protection step. Basic compounds are used to neutralize the reaction medium. A solution of strong or mild basic compounds are suitable for neutralization. Some examples of these basic compounds are ammonia, ammonium hydroxide, ammonium carbonate, ammonium bicarbonate sodium bicarbonate, sodium carbonate, sodium hydroxide, potassium bicarbonate, potassium carbonate, potassium hydroxide, calcium bicarbonate, calcium hydroxide, calcium carbonate, magnesium hydroxide, magnesium carbonate, magnesium bicarbonate, etc.

Accordingly, the acid is added to the solution of compound of Formula (XXI) in organic solvent and the de-protection reaction is allowed to proceed for about 1 hour at 15 to 40°C, preferably for 20-50 minutes at 20-35°C, most preferably for 30-40 minutes at 25-30°C. Also, the reaction is performed at higher or lower temperatures such as any temperature between 15 and 40°C if the reaction time is adapted accordingly. After completion of the reaction, a solution of the base compound is added to the reaction mixture.

Hydrochloric acid as de-protecting agent, dichloromethane or ethanol as organic solvent and aqueous sodium hydroxide or potassium hydroxide as base are used for neutralization. The de-protected compound of (R)-N-benzyl-2-amino-3-methoxypropionamide of Formula (XI) is then isolated from the reaction mixture and optionally purified.

Compound of Formula (XI) is acetylated to produce the Lacosamide of Formula I. Acetic anhydride, acetyl chloride, acetic acid or the like and derivatives thereof are used as an acetylating agent. The acetylation is performed in the presence or absence of a base. The base used is nitrogen-containing base selected from pyridine, dimethylaminopyridine, sodium acetate. The acetylation reaction is performed in presence of solvent selected from dichloromethane, toluene, ethyl acetate, water or mixture thereof.

Base is added to the solution of compound of Formula (XI) in an organic solvent and acetylating agent is then slowly added to the mixture. The reaction is allowed to proceed for up to 2 hours at temperature ranging from 5 to 40°C. Lacosamide produced is then isolated from the reaction mixture and purified.

Acetic anhydride as acetylating agent, dichloromethane, chloroform, ethyl acetate, isopropyl acetate or water as solvent and pyridine as base is used for the acetylation.
In another embodiment, the present invention further provides a process for the purification of Lacosamide of Formula (I).

The process comprises dissolving crude Lacosamide in a solvent selected from dichloromethane, isopropyl acetate, di-n-butyl ether, water and mixtures thereof, precipitating Lacosamide Form I by cooling the solution to about 0-5°C, and isolating crystalline Lacosamide Form 1.

Optionally, the crude Lacosamide is dissolved in a solution at a temperature from about 65 to 70°C to about the boiling temperature of the solvent. Optionally, the Lacosamide Form I is isolated by filtration. Optionally, the solution is treated with carbon, followed by filtration to remove insoluble material. The step of cooling the reaction is performed by cooling the solution to a temperature from about -10°C to 25°C temperature. The solvent is selected from dichloromethane, isopropyl acetate, di-n-butyl ether, water and mixtures thereof.

It has been observed that purification of crude Lacosamide using above solvents results in pure crystalline Lacosamide Form I, having (S)-enantiomer less than 0.1% by HPLC analysis.

The following examples are provided to illustrate the invention and are merely for illustrative purpose only and should not be construed to limit the scope of the invention.

EXAMPLE-1

Step 1:

Preparation of (R)-N-benzyl-2-N-Boc-amino-3-hydroxypropionamide
Method a:

N-Boc-D-Serine (32.8 g, 0.1599 mol) was suspended in methylene chloride (160 ml) and cooled to < -5°C. Isobutyl chloroformate (22.3 g, 0.1632 mol) was added to the above suspension at a temperature <-5°C and the resultant mixture was aged for 5-10 min at <-5°C. N-Methyl morpholine (16.5 g, 0.1631 mol) was added in 10-15 min at <-5°C. The resultant solution was aged for 30-40 min at <-5°C. Benzyl amine (17.7 g, 0.1652 mol) was added at <-5°C in 10-15 min. The mixture was aged for 70-80 min at <0°C, followed by successively washed with water (70 ml), IN HC1 (70 ml), 8% sodium bicarbonate (70 ml) and DM water (70 ml) to produce (R)-N-benzyl-2-N-Boc-amino-3-hydroxypropionamide. HPLC purity: -87%, Chiral Purity 99.2%.

Method b:

N-Boc-D-Serine (40 g, 0.1949 mol) was suspended in methylene chloride (125 ml) and cooled to <5°C. N-methylmorpholine (20.5 g, 0.2006 mol) was added in 5-10 min at <5°C and the resulting mixture was aged for 10-15 min to get clear solution. The solution was added to a solution of isobutyl chloroformate (27.4 g, 0.2006 mol) in methylene chloride (125 ml) at <-8°C in 60-70 min. The resulting solution was aged for 10-15 min at <-8°C and benzyl amine (21.3 g, 0.1987 m) was added at <-8°C in 20-30 min and aged for 60-70 min at <-5°C, followed by successively washed with water (80 ml), IN HC1 (80 ml), 8% sodium bicarbonate (80 ml) and DM water (80 ml) to produce (R)-N-Benzyl-2-N-Boc-amino-3-hydroxypropionamide in methylene chloride. HPLC purity: 93.31%, Chiral Purity 99.5%.

Step 2:

Production of (R)-N-benzyl-2-N-Boc-amino-3-methoxypropionamide
(R)-N-Benzyl-2-N-Boc amino-3-hydroxypropionamide solution prepared as per the method b was cooled to < 5°C and potassium hydroxide (17.6 g, 0.3136 mol) was added at <5°C. The resulting suspension was aged for 5-10 min at <5°C and dimethyl sulfate (29.6 g, 0.2346 mol) was added at <5°C in 10-15 min. The resulting mixture was aged for 3-5 h at <5°C. Water (80 ml) was added to the suspension and separated the phases. The organic layer was washed with a solution of citric acid (20.0 g) in DM water (80 ml) to produce (R)-N-benzyl-2-N-Boc-amino-3-methoxypropionamide solution in methylene chloride with HPLC purity (90%), Chiral purity (98%). The purity of the crude compound can be optionally improved by crystallization from a mixture of hexane and ethyl acetate.

Step 3:

Production of (R)-2-amino-N-benzyl-3-methoxypropionamide (R)-N-Benzyl-2-N-Boc-amino-3-methoxypropionamide solution in methylene chloride was concentrated till the solution volume was half of the original volume at 35-40°C under reduced pressure. Hydrochloric acid (36%, 55 ml, 0.6137 mol) was added at 25-30°C and the resulting mixture was aged for 60-90 min at 25-30°C. Water (60 ml) was added and the phases were separated. The aqueous phase was washed with methylene chloride (50 ml). The aqueous layer was basified to pH 10-11 with 30% sodium hydroxide at 25-30°C and saturated with sodium chloride (-20.0 g). The aqueous layer was extracted with methylene chloride (2 x 100 ml) and the combined organic layer was dried over anhydrous sodium sulfate. Methylene chloride was distilled off at 35-40°C under diminished pressure to get oily mass. Yield: 40.0 g, HPLC purity: -94%, Chiral purity: > 98%.

Step 4:

Preparation of (R)-N-Benzyl-2-acetamido-3-methoxypropionamide (Lacosamide)
(R)-N-Benzyl-2-amino-3-methoxypropionamide (35 g, 0.1681 mol) was dissolved in DM water (400 ml) at ambient temperature. The solution was cooled to 5-10°C, followed by pyridine (1.76 g, 0.0222 mol) and acetic anhydride (21.5 g, 0.2106 mol) were added at 5-10°C in 15-20 min. The solution was stirred for 30-40 min at 5-10°C and raised to room temperature (25-30°C) in over 30 min. The solution was further stirred for 30-40 min at room temperature (25-30°C). The compound was extracted with methylene chloride (2 x 200 ml). The organic layer was dried over by sodium sulfate for 10-15 min and solvent was completely recovered under vacuum at 35-40°C to get solid product. The solid was suspended in isopropyl acetate (200 ml) and stirred the suspension for 60-70 min at room temperature (25-30°C). Filtered the product and washed with isopropyl acetate. Yield: 30 g, Chiral purity. 99.5%.

Example-2

Purification of Lacosamide

Method a:

Lacosamide (6.5 g) was suspended in DM water (65 ml) at 25-30°C, temperature was raised to 65-70°C and stirred the mass for 60-70 min at 65-70°C. The solution was cooled to 30-35°C in 40-50 min. Further, the solution was cooled to 0-5°C in 30-40 min and the suspension was stirred for 40-50 min at 0-5°C. The compound was filtered and washed with prechilled water (10 ml, 0-5°C). The compound was dried at 40-50°C under diminished pressure till to get constant weight. Yield: 3.5 g, Chiral purity: 99.5%, HPLC purity: 99%.

Method b:

Lacosamide (30 g) was suspended in isopropyl acetate (150 ml) at 25-30°C, temperature was raised to 40-45°C and stirred the suspension for 60-70 min at 40-45°C. The product was filtered and washed with isopropyl acetate (2 x 45 ml). The compound was dried at 40-50°C under diminished pressure to constant weight. Yield: 25 g, Chiral purity: 99.97%, HPLC purity: 99.3%.

WE CLAIM

1. A process for the preparation of Lacosamide of Formula I; which comprises:

(i) O-methylation of a compound of Formula (XX); in the presence of a methylating agent and a base to produce Formula (XXI), with proviso that the O-methylation is not carried out in the presence of silver oxide;

(ii) deprotecting the compound of Formula (XXI) to produce a compound of Formula (XI);

(iii) acetylating the compound of Formula (XI) to produce Lacosamide of Formula (1).

2. The process according to claim 1, wherein the methyiating agent used in O-methylation step (i) is selected from methyl iodide, methyl chloride, methyl bromide, methyl fluoride, dimethyl sulfate, trimethyl silyldiazomethane, dimethyl sulfoxide (DMSO) or mixtures thereof.

3. The process according to claim 1, wherein the base used in O-methylation step (i) is selected from sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate or mixtures thereof.

4. The process according to claim 1, wherein the O-methylation step (i) and acetylation step (iii) are carried out in the presence of a solvent selected from tetrahydrofuran (THF), dichloromethane (MDC), dimethyl sulfoxide (DMSO), acetonitrile (MeCN), ethyl acetate , acetone, monoglyme, diglyme or mixtures thereof.

5. The process according to claim 1, wherein the de-protection in step (ii) is carried out in the presence of strong acid selected from hydrochloric acid, sulphuric acid, trifluoroacetic acid and mixtures thereof and mild acid is selected from acetic acid, oxalic acid, tartaric acid, phosphoric acid (H3PO4), sodium hydrogen phosphate (Na2HP04) and mixtures thereof.

6. The process according to claim 1, wherein an acetylating agent used in step (iii) is selected from acetic anhydride, acetyl chloride, acetic acid or the like and derivatives thereof.

7. The process according to claim 1, wherein the acetylation is carried out in the presence or absence of a base selected from triethylamine, pyridine, dimethylaminopyridine, N-Methylmorpholine and mixture thereof.

8. The process according to claim 1, wherein the compound of formula (XX) is prepared by a process, comprising: reacting a compound of Formula (XIX);

wherein, R represents N-protecting group;

with benzylamine in the presence of a base and an activator of the carboxyl group in a solvent to produce a compound of Formula (XX);

9. The process according to claim 8, wherein the base is selected from triethylamine, diisopropylethylamine, l,8-diazabicyclo-[5.4.0]undec-7-ene, 4-methylmorpholine, sodium carbonate, sodium bicarbonate, potassium bicarbonate, calcium carbonate and calcium bicarbonate or mixtures thereof; the activator of the carboxyl is selected from carbodiimide, isobutyl chloroformate, N,N-carbonyldiimidazole, ethylchloroformate and methylchloroformate or mixtures thereof and the solvent is selected from halogenated solvents such as dichloromethane, ethylene dichloride, and chloroform; ether, toluene, ethyl acetate or mixtures thereof.

10. A process for the purification of Lacosamide of Formula (I), which comprises:

(i) preparing a solution of crude Lacosamide in a solvent selected from isopropyl
acetate, di-n-butyl ether, dichloromethane, water and mixtures thereof optionally,
filtering the solution of step (i);

(ii) precipitating Lacosamide Form I by cooling the solution; (iii) isolating pure Lacosamide in crystalline Form I.