methyl 4-chloro-3-hydroxybutanoate

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

Procedure: To a mixture of methyl 4-chloro-3-hydroxybutyrate (5 g, 33 mmol), and methyl isobutyl ketone (40 ml) are added sodium azide (2.3 g, 36 mmol) and 4-dimethylaminopyridine (403 mg, 3.3 mmol) and the mixture was refluxed under stirring for 11 hours. After cooling the salt was filtered off and the solvent was distilled off under vacuo and there was obtained methyl 4-azido-3-hydroxybutyrate (5.5 g) as a crude product. And followed by the same procedure as in example 1, there was obtained 4-hydroxy-2-pyrrolidone (2.3 g, 23 mmol, yield:70%). When the above reaction was carried out in the absence of 4-dimethylaminopyridine, it took more than 120 hours to detect the disappearance of the starting materials on gas chromatography. the mixture was refluxed After cooling the salt was filtered off the solvent was distilled off under vacuo

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

Procedure: To a mixture of methyl 4-chloro-3-hydroxybutyrate (5 g, 33 mmol), and methyl isobutyl ketone (40 ml) are added sodium azide (2.3 g, 36 mmol) and 4-dimethylaminopyridine (403 mg, 3.3 mmol) and the mixture was refluxed under stirring for 11 hours. After cooling the salt was filtered off and the solvent was distilled off under vacuo and there was obtained methyl 4-azido-3-hydroxybutyrate (5.5 g) as a crude product. And followed by the same procedure as in example 1, there was obtained 4-hydroxy-2-pyrrolidone (2.3 g, 23 mmol, yield:70%). When the above reaction was carried out in the absence of 4-dimethylaminopyridine, it took more than 120 hours to detect the disappearance of the starting materials on gas chromatography. the mixture was refluxed After cooling the salt was filtered off the solvent was distilled off under vacuo

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

Procedure: In 10 ml of ethanol, 1.11 g (10 m.moles) of glycinamide hydrochloride, 1.06 g (10 m.moles) of sodium carbonate, and 1.53 g (10 m.moles) of methyl 4-chloro-3-hydroxybutyrate were stirred and refluxed simultaneously for 20 hours. After completion of the reaction, the warm reaction mixture was filtered to expel inorganic salts. The filtrate was analyzed by gas chromatography (Fluoxylate-K 1% Uniport HP 100/120, column length 0.5 m and column temperature 220° C., RT 2.8 min) (hereinafter referred to as "GC" for short). Consequently, the reaction was found to have produced oxiracetam in a yield of 75%. The filtrate was concentrated, dissolved in a small amount of water, and poured on a bed of 40 ml of Amberlite IR-120 (--SO3H form) (tradename: Rohm & Haas Co.). The adsorbate was eluted with water. The eluate was fractionated, with the first and second fractions discarded and the third and following fractions were collected. The collected fractions were concentrated. The concentrate was dissolved in methanol and the solution was ice cooled ad crystallized with crystals of oxiracetam used as mother crystals. The produced crystals were collected and vaccum dried, to afford 0.55 g (yield of isolation 35%) of oxiracetam, having a melting point of 155° to 160° C. (as compared with 161° to 163° C. reported in the specification of Japanese Patent Publication Sho 58-22,034/1983). refluxed simultaneously for 20 hours After completion of the reaction the warm reaction mixture was filtered was analyzed by gas chromatography (Fluoxylate-K 1% Uniport HP 100/120, column length 0.5 m and column temperature 220° C., RT 2.8 min)

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

Procedure: To a mixture of methyl 4-chloro-3-hydroxybutyrate (5 g, 33 mmol), and methyl isobutyl ketone (40 ml) are added sodium azide (2.3 g, 36 mmol) and 4-dimethylaminopyridine (403 mg, 3.3 mmol) and the mixture was refluxed under stirring for 11 hours. After cooling the salt was filtered off and the solvent was distilled off under vacuo and there was obtained methyl 4-azido-3-hydroxybutyrate (5.5 g) as a crude product. And followed by the same procedure as in example 1, there was obtained 4-hydroxy-2-pyrrolidone (2.3 g, 23 mmol, yield:70%). When the above reaction was carried out in the absence of 4-dimethylaminopyridine, it took more than 120 hours to detect the disappearance of the starting materials on gas chromatography. the mixture was refluxed After cooling the salt was filtered off the solvent was distilled off under vacuo