C(O[C:4](=[O:30])[CH2:5][C:6]([CH:8]1[CH2:13][CH2:12][N:11]([C:14]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[O:15])[CH:10]([C:24]2[N:25]=[N:26][N:27]([CH3:29])[N:28]=2)[CH2:9]1)=[O:7])C.[OH-].[Na+].[NH2:33]O.Cl>CO.O>[CH3:29][N:27]1[N:26]=[N:25][C:24]([CH:10]2[CH2:9][CH:8]([C:6]3[O:7][NH:33][C:4](=[O:30])[CH:5]=3)[CH2:13][CH2:12][N:11]2[C:14]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[O:15])=[N:28]1
Benzyl 4-(3-ethoxy-3-oxopropanoyl)-2-(2-methyl-2H-tetrazol-5-yl)piperidine-1-carboxylate (0.499 g, 1.20 mmol) was dissolved in MeOH (6 mL) and cooled to −40° C. 3.8 M NaOH (0.316 mL, 1.20 mmol) dissolved in water (0.6 mL) was added and the reaction stirred at −40° C. for 40 min. Hydroxylamine (50% by weight in water, 0.074 mL, 1.20 mmol) was added and stirring continued for 3.5 h at −40° C. The reaction mixture was then added to a preheated 80° C. solution of 6 M HCl (6.01 mL, 36.03 mmol) and stirred for 20 min. The reaction mixture was partitioned between water and DCM. The aqueous phase was extracted twice with DCM and the combined organic phase was dried and evaporated. The compound was purified by preparative HPLC on a Kromasil C8 column (10 μm 250×50 ID mm) using a gradient of 15-55% Acetonitrile in H2O/MeCN/NH3 95/5/0.2 buffer over 20 minutes with a flow of 100 mL/min. Benzyl 2-(2-methyl-2H-tetrazol-5-yl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (327 mg, 71%) was isolated. 1H NMR (400 MHz, cdcl3) δ 1.96-2.15 (m, 2H), 2.41 (dt, 1H), 2.64-2.74 (m, 1H), 3.12-3.19 (m, 1H), 3.61-3.72 (m, 1H), 4.07-4.20 (m, 4H), 5.13 (s, 2H), 5.43 (s, 1H), 5.58-5.64 (m, 1H), 7.25-7.41 (m, 5H). MS m/z 385 (M+H)+
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