C[O:2][C:3]([CH:5]1[CH2:9][N:8]([C@@H:10]([CH2:14][CH3:15])[C:11]([NH2:13])=[O:12])[C:7](=[O:16])[CH2:6]1)=O.[BH4-].[Na+].[NH4+].[Cl-].CC(C)=O>CCO.C(Cl)Cl>[OH:2][CH2:3][CH:5]1[CH2:9][N:8]([C@@H:10]([CH2:14][CH3:15])[C:11]([NH2:13])=[O:12])[C:7](=[O:16])[CH2:6]1
In a 2 l three necked flask fitted with mechanical stirrer and reflux condenser, under inert atmosphere, a solution of 133 g (583 mmoles, 1 eq) of (2S)-2-(4-methoxycarbonyl-2-oxo-1-pyrrolidinyl)butanamide 11 in 200 ml of EtOH is added to 300 ml of EtOH, and the mixture cooled down to 0° C. 66.2 g (1.74 mole, 12 eq) of solid NaBH4 are then added by portions over 1.5 hour, all the while maintaining the temperature between 2 and 4° C. After 2 hours, the temperature is raised to 12° C. for 1 hour, and lowered again to 2-4° C. 240 ml of a saturated solution of NH4Cl are added dropwise over 1 hour, followed by 120 ml of acetone, and the mixture is left overnight at room temperature. The mixture is filtered, the precipitate washed with 3×70 ml of EtOH and the combined organic fractions concentrated to dryness to give 148 g of crude 6. It is suspended in 300 ml of CH2Cl2 and stirred for 30 min, filtered, washed with 2×100 ml of CH2Cl2 and dried to give 114 g of pure 6, 98%.
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