Hydrochloric Acid → tert-butyl ((3R,4S,5S)-1-(3-aminopyridin-4-yl)-4-azido-5-methylpiperidin-3-yl)carbamate

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A solution of 4 M HCl in dioxane (30.0 equiv.) was added to tert-butyl (4-((3R,4S,5S)-4-azido-3-((tert-butoxycarbonyl)amino)-5-methylpiperidin-1-yl)pyridin-3-yl)(tert-butoxycarbonyl)carbamate (1.0 equiv.). The solution started to go homogeneous for a few minutes, but then a ppt formed and the solution went very thick. After sitting at rt for 1 hour, the volatiles were removed in vacuo and the solid was pumped on for 5 minutes on the high vac. To the residue was added CH2Cl2 (0.11 M), TEA (5.0 equiv.) and Boc2O (1.0 equiv.). The solution was left stirring at rt for 1 hr. The volatiles were removed in vacuo and the residue was partitioned between EtOAc and H2O. The organic layer was washed with Na2CO3(sat), NaCl(sat.), dried over MgSO4, filtered, concentrated and purified by ISCO SiO2 chromatography to yield tert-butyl ((3R,4S,5S)-1-(3-aminopyridin-4-yl)-4-azido-5-methylpiperidin-3-yl)carbamate in 33% yield. LC/MS (m/z)=348.2 (MH+), Rt=0.70 min. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.02-1.18 (m, 3 H), 1.36-1.54 (m, 10 H), 2.19 (qd, J=6.91, 3.91 Hz, 1 H), 2.57 (q, J=10.96 Hz, 2 H), 2.96 (d, J=9.00 Hz, 1 H), 3.20 (dd, J=11.15, 3.72 Hz, 1 H), 3.55-3.73 (m, 2 H), 3.90 (br. s., 1 H), 4.01 (br. s., 1 H), 4.81 (d, J=8.61 Hz, 1 H), 6.72-6.83 (m, 1 H), 7.96 (d, J=5.09 Hz, 1 H), 8.02 (s, 1 H).

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