[OH:1][CH2:2][C:3]1([CH3:7])[CH2:6][O:5][CH2:4]1.C([NH:15][CH:16]1[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]1)(OC(C)(C)C)=O.[CH3:22]CCP(=O)=O.C(N(CC)C(C)C)(C)C>C(Cl)Cl.O.O1CCCC1.O.O.O.O.O.O.[Ni](Cl)Cl>[NH2:15][CH:16]1[CH2:17][CH2:18][N:19]([CH2:22][C:2]([C:3]2([CH3:7])[CH2:6][O:5][CH2:4]2)=[O:1])[CH2:20][CH2:21]1.[NH2:15][CH:16]1[CH2:21][CH2:20][N:19]([C:2]([C:3]2([CH3:7])[CH2:6][O:5][CH2:4]2)=[O:1])[CH2:18][CH2:17]1A solution of 3-hydroxymethyl-3-methyloxetane (1.90 mL, 19.1 mmol) in methylene chloride (6 mL) was added to a solution of nickel (II) chloride hexahydrate (113 mg, 0.476 mmol) in water (2 mL). This mixture was cooled to 0° C. and bleach (127 mL) was added over a 30 min period via addition funnel. After 2 h the ice bath was removed and the reaction mixture was stirred at room temperature for an additional 2 h. 2M HCl (120 mL) was added and the solution was extracted with ether (4×200 mL). The combined extracts were dried over sodium sulfate and concentrated to a clear oil. A portion of this oil (1.00 g, 8.61 mmol) was dissolved in tetrahydrofuran (43 mL) and 4-(N-Boc-amino)-piperidine (2.07 g, 10.3 mmol) was added at room temperature. Propylphosphonic anhydride (6.99 mL, 50 wt. % in ethyl acetate, 11.2 mmol) and N,N-diisopropylethylamine (3.00 mL, 17.2 mmol) were added, and the reaction mixture was stirred for 24 h. The solution was partitioned between ethyl acetate (35 mL) and water (35 mL). The organic portion was washed with 0.2M HCl (10 mL), sat. sodium bicarbonate (35 mL), and brine (35 mL). The solution was then dried over sodium sulfate and concentrated. The crude material was purified by column chromatography on silica gel (0% to 100% methylene chloride in ethyl acetate). The resulting amide (213 mg, 0.714 mg) was diluted with methylene chloride (7 mL) and trifluoroacetic acid (1.8 mL) was added at room temperature. After 2 h the solution was concentrated and a 2M sodium hydroxide solution was added. The aqueous solution was extracted with ethyl acetate (3×10 mL). The combined extracts were dried over sodium sulfate and concentrated to give the title compound as a clear oil, (4-aminopiperidin-1-yl)(3-methyloxetan-3-yl)methanone, 68 mg (4% over three steps). 1H NMR (300 MHz, CD3OD) δ 4.95-4.88 (m, 2H), 4.48-4.38 (m, 1H), 4.38-4.31 (m, 2H), 3.19-2.96 (m, 2H), 2.94-2.81 (m, 1H), 2.81-2.66 (m, 1H), 1.93-1.81 (m, 2H), 1.67-1.60 (m, 3H), 1.36-1.15 (m, 2H).
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