[NH2:1][C@H:2]([C:4]([NH:6][C@H:7]([C:10]([OH:12])=[O:11])[CH2:8][OH:9])=[O:5])[CH3:3].FC1C([O:20][C:21](=O)[C@@H:22]2[CH2:26][C@@H:25]([OH:27])[CH2:24][N:23]2C(OC(C)(C)C)=O)=C(F)C(F)=C(F)C=1F.[ClH:40]>CN(C)C=O.C(O)(C)C>[ClH:40].[OH:27][C@H:25]1[CH2:24][NH:23][C@H:22]([C:21]([NH:1][C@H:2]([C:4]([NH:6][C@H:7]([C:10]([OH:12])=[O:11])[CH2:8][OH:9])=[O:5])[CH3:3])=[O:20])[CH2:26]1N-alanylserine (1.5 kg, 8.515 M) and Boc-trans-4-hydroxy-L-proline (3.72 kg) (prepared as described in step 2) were heated at 50° C. in dimethylformamide (15 L) for 3 hours. The solution was cooled to 20° C., treated with concentrated hydrochloric acid (7.5 L) and stirred at room temperature for 24 hours. The resulting slurry was diluted with isopropanol (30 L), stirred at room temperature for 30 minutes and then cooled to 0° C. for 1 hour. The solid was collected by filtration and washed with isopropanol (20 L). The solid was dried in vacuo at 40° C. to afford the title compound as a white crystalline solid.
불러오는 중…
