(2R)-2-acetamido-N-benzyl-3-hydroxypropanamide

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of N-benzyl-O-tert-butyl-N2-acetyl-D-serinamide (0.5 g) and dichloromethane (10 mL), aq. HCl 35% (5 mL) was added. The solution was stirred for 2 hours at room temperature for completion of reaction and after workup and crystallization gave solid 0.21 g N-benzyl-N2-acetyl-D-serinamide. after workup and crystallization

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of N-benzyl-O-tert-butyl-N2-acetyl-D-serinamide (0.5 g) and dichloromethane (10 mL), aq. HCl 35% (5 mL) was added. The solution was stirred for 2 hours at room temperature for completion of reaction and after workup and crystallization gave solid 0.21 g N-benzyl-N2-acetyl-D-serinamide. after workup and crystallization

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (R)-2-Acetamido-N-benzyl-3-hydroxypropionamide (25 g, 0.1059 mole) was suspended in 125 ml of acetonitrile at room temperature. To this was added aqueous sodium hydroxide solution (6.3 g in 15 ml, 0.158 mol) drop wise, followed by dimethyl sulfate (26.7 g, 0.211 mole) drop wise. The reaction mixture was stirred for one hour and concentrated under reduced pressure. The resulting residue was dissolved in 200 ml dichloromethane and the solution washed with water (100 ml×3). The organic layer was treated with 1 g charcoal and stirred for one hour. It was filtered and the filtrate was concentrated under reduced pressure. The solid residue obtained was dissolved in acetone and precipitated by adding diisopropyl ether to obtain Lacosamide. (18.5 g, Yield: 70%; chiral HPLC: 99.8% and chemical HPLC: 99.7%) concentrated under reduced pressure The resulting residue was dissolved in 200 ml dichloromethane the solution washed with water (100 ml×3) The organic layer was treated with 1 g charcoal stirred for one hour It was filtered the filtrate was concentrated under reduced pressure The solid residue obtained precipitated by adding diisopropyl ether

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: N-Acetyl-D-serine methyl ester (1.0 g, 0.0062 mole) was dissolved in benzylamine (1.32 g, 0.0124 mole) at 0-5° C. To this was added triethylamine (0.125 g, 0.00124 mole) at 0-5° C. The reaction mixture was heated and stirred at 60° C. for 12 hr, cooled to room temperature, 20 ml methyl tert-butyl ether added and stirred for 3 hr. The product was filtered and dried under vacuum to obtain (R)-2-acetamido-N-benzyl-3-hydroxy-propionamide. (1.0 g, Yield: 68.4%, HPLC:94.8%, Chiral HPLC: 81.2%), The reaction mixture was heated cooled to room temperature stirred for 3 hr The product was filtered dried under vacuum

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: N-Acetyl-D-serine methyl ester (25 g, 0.155 mole) was dissolved in benzylamine (33.2 g, 0.3101 mole) at 0-5° C. To this triethylamine (3.13 g, 0.031 mole) was added at 0-5° C. The reaction mixture was allowed to cool to room temperature and stirred for 12 hr. To the thick colorless precipitate formed 300 ml methyl tert-butyl ether was added and stirred for 6 hr. The product was filtered and dried under vacuum to obtain (R)-2-acetamido-N-benzyl-3-hydroxy-propionamide (34.03 g, Yield: 93%, HPLC: 98.9, Chiral HPLC: 98.8%) was added stirred for 6 hr The product was filtered dried under vacuum

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: N-Acetyl-D-serine methyl ester (1.0 g, 0.0062 mole) was dissolved in benzylamine (6.64 g, 0.062 mole) at 0-5° C. The reaction mixture was heated and stirred at 65° C. for 12 hr. The excess benzylamine was removed by distillation under vacuum at 90° C. to get a thick white solid. To this was added 10 ml of methyl tert-butyl ether and stirred for 2 hr at room temperature. The product was filtered and dried under vacuum to obtain (R)-2-acetamido-N-benzyl-3-hydroxy-propionamide (1.09 g, Yield 75%, HPLC: 92%, Chiral HPLC: 78%). The reaction mixture was heated The excess benzylamine was removed by distillation under vacuum at 90° C. to get a thick white solid stirred for 2 hr at room temperature The product was filtered dried under vacuum

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: N-Acetyl-D-serine methyl ester (25 g, 0.155 mole) was dissolved in benzylamine (33.2 g, 0.3101 mole) at 0-5° C. The reaction mixture was allowed to room temperature and stirred for 12 hr. To the thick colorless precipitate formed was added 300 ml methyl tert-butyl ether and stirred for 6 hr. The product was filtered and dried under vacuum to obtain (R)-2-acetamido-N-benzyl-3-hydroxy-propionamide (30.0 g, Yield: 82%, HPLC: 98.9, Chiral HPLC: 96.2%). was allowed to room temperature To the thick colorless precipitate formed stirred for 6 hr The product was filtered dried under vacuum

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (R)-2-Acetamido-N-benzyl-3-hydroxypropionamide (25 g, 0.1059 mole) was suspended in 125 ml of acetonitrile at room temperature. To this was added aqueous sodium hydroxide solution (6.3 g in 15 ml, 0.158 mol) drop wise, followed by dimethyl sulfate (26.7 g, 0.211 mole) drop wise. The reaction mixture was stirred for one hour and concentrated under reduced pressure. The resulting residue was dissolved in 200 ml dichloromethane and the solution washed with water (100 ml×3). The organic layer was treated with 1 g charcoal and stirred for one hour. It was filtered and the filtrate was concentrated under reduced pressure. The solid residue obtained was dissolved in acetone and precipitated by adding diisopropyl ether to obtain Lacosamide. (18.5 g, Yield: 70%; chiral HPLC: 99.8% and chemical HPLC: 99.7%) concentrated under reduced pressure The resulting residue was dissolved in 200 ml dichloromethane the solution washed with water (100 ml×3) The organic layer was treated with 1 g charcoal stirred for one hour It was filtered the filtrate was concentrated under reduced pressure The solid residue obtained precipitated by adding diisopropyl ether

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: N-Acetyl-D-serine methyl ester (1.0 g, 0.0062 mole) was dissolved in benzylamine (1.32 g, 0.0124 mole) at 0-5° C. To this was added triethylamine (0.125 g, 0.00124 mole) at 0-5° C. The reaction mixture was heated and stirred at 60° C. for 12 hr, cooled to room temperature, 20 ml methyl tert-butyl ether added and stirred for 3 hr. The product was filtered and dried under vacuum to obtain (R)-2-acetamido-N-benzyl-3-hydroxy-propionamide. (1.0 g, Yield: 68.4%, HPLC:94.8%, Chiral HPLC: 81.2%), The reaction mixture was heated cooled to room temperature stirred for 3 hr The product was filtered dried under vacuum

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: N-Acetyl-D-serine methyl ester (25 g, 0.155 mole) was dissolved in benzylamine (33.2 g, 0.3101 mole) at 0-5° C. To this triethylamine (3.13 g, 0.031 mole) was added at 0-5° C. The reaction mixture was allowed to cool to room temperature and stirred for 12 hr. To the thick colorless precipitate formed 300 ml methyl tert-butyl ether was added and stirred for 6 hr. The product was filtered and dried under vacuum to obtain (R)-2-acetamido-N-benzyl-3-hydroxy-propionamide (34.03 g, Yield: 93%, HPLC: 98.9, Chiral HPLC: 98.8%) was added stirred for 6 hr The product was filtered dried under vacuum

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: N-Acetyl-D-serine methyl ester (1.0 g, 0.0062 mole) was dissolved in benzylamine (6.64 g, 0.062 mole) at 0-5° C. The reaction mixture was heated and stirred at 65° C. for 12 hr. The excess benzylamine was removed by distillation under vacuum at 90° C. to get a thick white solid. To this was added 10 ml of methyl tert-butyl ether and stirred for 2 hr at room temperature. The product was filtered and dried under vacuum to obtain (R)-2-acetamido-N-benzyl-3-hydroxy-propionamide (1.09 g, Yield 75%, HPLC: 92%, Chiral HPLC: 78%). The reaction mixture was heated The excess benzylamine was removed by distillation under vacuum at 90° C. to get a thick white solid stirred for 2 hr at room temperature The product was filtered dried under vacuum

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: N-Acetyl-D-serine methyl ester (25 g, 0.155 mole) was dissolved in benzylamine (33.2 g, 0.3101 mole) at 0-5° C. The reaction mixture was allowed to room temperature and stirred for 12 hr. To the thick colorless precipitate formed was added 300 ml methyl tert-butyl ether and stirred for 6 hr. The product was filtered and dried under vacuum to obtain (R)-2-acetamido-N-benzyl-3-hydroxy-propionamide (30.0 g, Yield: 82%, HPLC: 98.9, Chiral HPLC: 96.2%). was allowed to room temperature To the thick colorless precipitate formed stirred for 6 hr The product was filtered dried under vacuum