(2R)-2-(2-oxopyrrolidin-1-yl)butanamide

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of (R)-alpha-ethyl-2-oxo-1-pyrrolidineacetic acid (35 g, 0.20 mol) in methylene chloride (225 ml) was cooled to 0° C. and triethylamine (41 g, 0.40 mol) and methanesulfonyl chloride (29 g, 0.26 mol) were added dropwise. The mixture was stirred at 0° C. for 30 min., then a stream of ammonia was purged in the solution at 0° C. for 2 hours. The insoluble solids were filtered and the filtrate was concentrated. The product was recrystallized from methyl isobutyl ketone to give 27.5 g (78%) of (R)-alpha-ethyl-2-oxo-1-pyrrolidineacetamide. a stream of ammonia was purged in the solution at 0° C. for 2 hours The insoluble solids were filtered the filtrate was concentrated The product was recrystallized from methyl isobutyl ketone

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

Procedure: 6.2 g (0.03 mole) of (R)-N-[1-(aminocarbonyl)propyl]-4-chlorobutanamide and 0.484 g (0.0015 mole) of tetrabutylammonium bromide are mixed in 42 ml of dichloromethane at 0° C. under a nitrogen atmosphere. 2.02 g (0.036 mole) of potassium hydroxide powder are added over 30 minutes at such a rate that the temperature of the reaction mixture does not exceed +2° C. The mixture is stirred for 15 minutes and then allowed to return to ambient temperature. The insoluble material is filtered off and the filtrate concentrated under reduced pressure. The residue obtained is stirred in 25 ml of carbon tetrachloride for 30 minutes, and then filtered off and dried. The product is recrystallized in 45 ml of ethyl acetate in the presence of 1.7 g of 0,4 nm molecular sieve. The latter is removed by hot filtration to give 3.85 g of (R)-alpha-ethyl-2-oxo-1-pyrrolidineacetamide. Melting point: 116°-118° C. [alpha]D25 : +89.8° (c=1, acetone). Yield: 75.4%. does not exceed +2° C to return to ambient temperature The insoluble material is filtered off the filtrate concentrated under reduced pressure The residue obtained filtered off dried The product is recrystallized in 45 ml of ethyl acetate in the presence of 1.7 g of 0,4 nm molecular sieve The latter is removed by hot filtration

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

Procedure: 6.2 g (0.03 mole) of (R)-N-[1-(aminocarbonyl)propyl]-4-chlorobutanamide and 0.484 g (0.0015 mole) of tetrabutylammonium bromide are mixed in 42 ml of dichloromethane at 0° C. under a nitrogen atmosphere. 2.02 g (0.036 mole) of potassium hydroxide powder are added over 30 minutes at such a rate that the temperature of the reaction mixture does not exceed +2° C. The mixture is stirred for 15 minutes and then allowed to return to ambient temperature. The insoluble material is filtered off and the filtrate concentrated under reduced pressure. The residue obtained is stirred in 25 ml of carbon tetrachloride for 30 minutes, and then filtered off and dried. The product is recrystallized in 45 ml of ethyl acetate in the presence of 1.7 g of 0,4 nm molecular sieve. The latter is removed by hot filtration to give 3.85 g of (R)-alpha-ethyl-2-oxo-1-pyrrolidineacetamide. Melting point: 116°-118° C. [alpha]D25 : +89.8° (c=1, acetone). Yield: 75.4%. does not exceed +2° C to return to ambient temperature The insoluble material is filtered off the filtrate concentrated under reduced pressure The residue obtained filtered off dried The product is recrystallized in 45 ml of ethyl acetate in the presence of 1.7 g of 0,4 nm molecular sieve The latter is removed by hot filtration

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To the crude methyl-(R)-4-(1-carbamoylpropylamino)butyrate (VIf) in toluene (20 ml) is added 2-hydroxypyrridine (50 mg, 10 mol %). The mixture is heated to 80° C. until complete conversion. After 16 hours (GC: 100% conversion) the mixture is concentrated to dryness to yield (R)-2-(2-oxopyrrolidin-1-yl)butyramide (0.28 g, 1.6 mmol, 30%, yield determination by GC assay from pure standard). After 16 hours (GC: 100% conversion) the mixture is concentrated to dryness

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

Procedure: 6.2 g (0.03 mole) of (R)-N-[1-(aminocarbonyl)propyl]-4-chlorobutanamide and 0.484 g (0.0015 mole) of tetrabutylammonium bromide are mixed in 42 ml of dichloromethane at 0° C. under a nitrogen atmosphere. 2.02 g (0.036 mole) of potassium hydroxide powder are added over 30 minutes at such a rate that the temperature of the reaction mixture does not exceed +2° C. The mixture is stirred for 15 minutes and then allowed to return to ambient temperature. The insoluble material is filtered off and the filtrate concentrated under reduced pressure. The residue obtained is stirred in 25 ml of carbon tetrachloride for 30 minute and then filtered off and dried. The product is recrystallized in 45 ml of ethyl acetate in the presence of 1.7 g of 0,4 nm molecular sieve. The latter is removed by hot filtration to give 3.85 g of (R)-alpha-ethyl-2-oxo-1-pyrrolidineacetamide. does not exceed +2° C to return to ambient temperature The insoluble material is filtered off the filtrate concentrated under reduced pressure The residue obtained filtered off dried The product is recrystallized in 45 ml of ethyl acetate in the presence of 1.7 g of 0,4 nm molecular sieve The latter is removed by hot filtration

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of (R)-alpha-ethyl-2-oxo-1-pyrrolidineacetic acid (35 g, 0.20 mol) in methylene chloride (225 ml) was cooled to 0° C. and triethylamine (41 g, 0.40 mol) and methanesulfonyl chloride (29 g, 0.26 mol) were added dropwise. The mixture was stirred at 0° C. for 30 min., then a stream of ammonia was purged in the solution at 0° C. for 2 hours. The insoluble solids were filtered and the filtrate was concentrated. The product was recrystallized from methyl isobutyl ketone to give 27.5 g (78%) of (R)-alpha-ethyl-2-oxo-1-pyrrolidineacetamide. a stream of ammonia was purged in the solution at 0° C. for 2 hours The insoluble solids were filtered the filtrate was concentrated The product was recrystallized from methyl isobutyl ketone