[NH2:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][N:4]([C:8]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:9])[C@@H:3]1[CH3:18].[H-].[Na+]>C1COCC1.CCOC(C)=O.O>[CH3:18][C@@H:3]1[C@H:2]([N:1]2[CH2:2][CH2:3][NH:4][C:8]2=[O:9])[CH2:7][CH2:6][CH2:5][N:4]1[C:8]([O:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:9](2R,3R)-Benzyl 3-amino-2-methylpiperidine-1-carboxylate (323, 610 mg, 2.46 mmol) was dissolved in 10 mL dry THF. To it was added 2-chloroethyl isocyante (210 μL, 2.46 mmol), and the mixture was stirred at RT for 2 hours. To it was added NaH (60% in mineral oil, 120 mg, 2.95 mmol) and the mixture was stirred for overnight. Another batch of NaH (120 mg, 2.95 mmol) was then added to drive the cyclization to completion in overnight. The mixture was diluted with 150 mL EtOAc and 50 mL water. The organic phase was separated, washed with water, dried, concentrated in vacuo, and subjected to silica flash column using 0 to 4% MeOH in DCM to isolate (2R,3R)-benzyl 2-methyl-3-(2-oxoimidazolidin-1-yl)piperidine-1-carboxylate (354, 490 mg, 63%) as a white solid.
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