[OH:1][CH2:2][CH:3]1[CH2:7][N:6]([C@@H:8]([CH2:12][CH3:13])[C:9]([NH2:11])=[O:10])[C:5](=[O:14])[CH2:4]1.C(N(CC)CC)C.[CH3:22][S:23](Cl)(=[O:25])=[O:24]>C(Cl)Cl>[CH3:22][S:23]([O:1][CH2:2][CH:3]1[CH2:4][C:5](=[O:14])[N:6]([C@H:8]([C:9]([NH2:11])=[O:10])[CH2:12][CH3:13])[CH2:7]1)(=[O:25])=[O:24]In a 4 l three necked flask fitted with mechanical stirrer, dropping funnel and reflux condenser under inert atmosphere, 114 g (569 mmoles, 1 eq) of (2S)-2-[4-hydroxymethyl)-2-oxo-1-pyrrolidinyl]butanamide 6 are dissolved in 2 l of CH2Cl2 and cooled down to 0° C. 158.5 ml (115 g, 2 eq) of dry triethylamine are added in one portion, followed by dropwise addition of a solution of 66.3 ml (96.2 g, 1.5 eq) of methanesulfonyl chloride in 190 ml of CH2Cl2 over 1 hour, all the while maintaining the temperature below 4° C. After 4 hours, 7.5 ml of methanesulfonyl chloride and 15 ml of triethylamine are added and the mixture is kept overnight in the refrigerator. The mixture is filtered, the residue washed with CH2Cl2 and the combined organic phases concentrated to dryness to give 216 g of crude 37. It is purified by Prep LC in several batches (1 kg SiO2, CH2Cl2/EtOH, 100:0->96:4) to give 109 g of pure 37, 69%.
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