[CH3:1][C:2]([CH3:24])([CH3:23])[CH2:3][CH2:4][C@H:5]1[CH2:10][C@@H:9]([C:11](=[O:18])[CH2:12][C:13](OCC)=[O:14])[CH2:8][CH2:7][N:6]1[C:19]([O:21][CH3:22])=[O:20].[OH-].[Na+].Cl.[NH2:28]O.Cl>CO.CO.O.O>[CH3:1][C:2]([CH3:24])([CH3:23])[CH2:3][CH2:4][C@H:5]1[CH2:10][C@@H:9]([C:11]2[O:18][NH:28][C:13](=[O:14])[CH:12]=2)[CH2:8][CH2:7][N:6]1[C:19]([O:21][CH3:22])=[O:20]A solution of cis-methyl 2-(3,3-dimethylbutyl)-4-(3-ethoxy-3-oxopropanoyl)piperidine-1-carboxylate (1.78 g, 5.22 mmol) in MeOH (3.9 mL) was added to a solution of NaOH (288 mg, 7.2 mmol) in MeOH/H2O (4.4 mL/0.3 mL) at −30° C. After 10 min was added hydroxylamine hydrochloride (726 mg, 10.45 mmol) and NaOH (418 mg, 10.45 mmol) in MeOH (5.2 mL) and H2O (5.2 mL). Stirring was continued at −30° C. for 30 min. The reaction solution was poured into 6 M HCl (7.7 mL) at 80° C. and heated at 80° C. for 1 h. Concentration of the organic solvent and extraction with DCM (×2), drying using a phase separator and evaporation gave an orange oil. The compound was purified by preparative HPLC on a Kromasil C8 column (10 μm 250×50 ID mm) using a gradient of 30-60% Acetonitrile in H2O/MeCN/FA 95/5/0.2 buffer over 30 minutes with a flow of 100 mL/min. Cis-methyl 2-(3,3-dimethylbutyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (717 mg, 44%) was isolated. 1H NMR (400 MHz, cdcl3) δ 0.79 (s, 9H), 1.01-1.19 (m, 2H), 1.23-1.48 (m, 2H), 1.83-1.96 (m, 2H), 1.98-2.11 (m, 2H), 2.94-3.04 (m, 1H), 3.09-3.19 (m, 1H), 3.70 (s, 3H), 3.91-4.06 (m, 2H), 5.71 (d, 1H). MS m/z 311 (M+H)+
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