[S:1](Cl)([C:4]1[CH:12]=[CH:11][C:7]([N+:8]([O-:10])=[O:9])=[CH:6][CH:5]=1)(=[O:3])=[O:2].[C:14](#[N:16])[CH3:15].N[C@H](CO)C.C(OCC)(=O)C>N1C=CC=CC=1>[S:1]([N:16]1[CH2:15][CH2:14]1)([C:4]1[CH:12]=[CH:11][C:7]([N+:8]([O-:10])=[O:9])=[CH:6][CH:5]=1)(=[O:3])=[O:2]A 100 gallon glass-lined vessel, fitted with mechanical stirrer, addition funnel, nitrogen inlet and temperature probe, was charged with nosylchloride (52.7 kg) and acetonitrile (75L) at room temperature under nitrogen. The slurry was cooled to about 0° C. A solution of L-alaninol (7) (7.5 kg) in pyridine (32L) was added over about an hour maintaining the reaction temperature less than 10° C. during the addition, and then the mixture was aged for about two hours at about 3° C. to 5° C. Ethyl acetate (188L) and water (75L) were added and the phases were mixed. The lower aqueous layer was removed and the organic layer was washed with 1M citric acid (2×37.5L) and water (37.5L). The organic layer was cooled to about 15° C. and water (37.5L) was added. Hunig's base (N,N-diisopropylethylamine) (27L) was added for over 30 minutes. The two-phase mixture was aged at 20° C. for about an hour to complete the cyclization, and then the lower aqueous layer was removed and extracted with ethyl acetate (37.5L). The combined organic solutions were washed with 1M citric acid (2×37.5L) and water (2×37.5L). The organic layer was dried by concentration at reduced pressure and temperature at about 15° C.˜20° C. with concurrent addition of isopropylacetate (IPAC) to maintain the constant volume at about 100L. The solvent switch was completed when EA level was <5% by GC or HPLC analysis. The slurry was cooled to about 3° C. for an hour and then filtered. The cake was washed with IPAC (30L) and the solid was dried in air, which afforded about 84% isolated yield for the compound (8) (23.7 kg, 97 wt %).
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