(2S)-2-aminobutanamide

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

Procedure: 2-Hydroxy-5-oxo-2,5-dihydro-furan-3-carboxylic acid methyl ester (3.08 g) in methanol (40 ml) is added to a solution of (2S)-2-aminobutyramide (2.0 g) in methanol (30 ml) in a hydrogenation reactor and the mixture is maintained for at least 2 hours at room temperature. Then Pd/C catalyst (10 w/w %; Johnson Matthey 5% Pd on carbon—type 87L) is added and hydrogen introduced into the system under pressure. The temperature is kept at 40° C. maximum and the hydrogen pressure between 4 bar and 5 bar, followed by stirring for at least 20 hours following the initial reaction. The solution is then cooled between 15° C. and 25° C. and filtered to remove the catalyst. The solvent is evaporated under vacuum and the resulting yellow product is purified by preparative liquid chromatography (eluent: dichloromethane/methanol (95:5)) (Yield 43%). is kept at 40° C. reaction The solution is then cooled between 15° C. and 25° C. filtered to remove the catalyst The solvent is evaporated under vacuum the resulting yellow product is purified by preparative liquid chromatography (eluent: dichloromethane/methanol (95:5)) (Yield 43%)

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

Procedure: Example 1 is repeated except that in step 1.1 a solution of (2S)-2-aminobutyramide.HCl in isopropanol is used (27.72 g, 1.2 equivalent), which is neutralised with a NH3/isopropanol solution (3.4-3.7 mol/L). The resulting ammonium chloride is removed from this solution by filtration and the solution is directly used for reaction with 5-hydroxy-4-n-propyl-furan-2-one (23.62 g, 1.0 equivalent) without intermediate drying of the (2S)-2-aminobutyramide solution. Yield after separation of the two diastereoisomers and recrystallisation: approximately 84%. The resulting ammonium chloride is removed from this solution by filtration drying of the (2S)-2-aminobutyramide solution Yield after separation of the two diastereoisomers and recrystallisation