2-(Benzylamino)-2-methylpropan-1-ol → Tert-butyl 4-((benzyl(1-hydroxy-2-methylpropan-2-yl)amino)methyl)-4-hydroxypiperidine-1-carboxylate

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2-(Benzylamino)-2-methyl-propan-1-ol hydrochloride (539 mg, 2.50 mmol) was treated with aqueous sodium hydroxide (50 mL of 2 M, 100 mmol), then diethyl ether (50 mL) was added to the solution and stirred for 3 min. The organic layer was separated, washed with brine, dried over Na2SO4, filtered and concentrated in vacuo to provide the 2-(benzylamino)-2-methyl-propan-1-ol free base as a white powder. The 2-(benzylamino)-2-methyl-propan-1-ol (2.50 mmol) and tert-butyl 1-oxa-6-azaspiro[2.5]octane-6-carboxylate (500 mg, 2.344 mmol) were dissolved in ethanol (2 mL) and the reaction mixture was heated in a sealed tube at 100° C. for 48 h. The ethanol was evaporated and the crude material purified by silica gel column chromatography (1-100% ethyl acetate/hexanes) to provide tert-butyl 4-((benzyl(1-hydroxy-2-methylpropan-2-yl)amino)methyl)-4-hydroxypiperidine-1-carboxylate as white powder (551 mg, 60%). ESI-MS m/z calc. 392.5. Found 373.3 (M+1)+; Retention time: 1.14 minutes (3 min run). 1H NMR (400 MHz, DMSO-d6) δ 7.43 (d, J=7.4 Hz, 2H), 7.24 (t, J=7.6 Hz, 2H), 7.13 (t, J=7.3 Hz, 1H), 4.66 (t, J=5.1 Hz, 1H), 4.43 (s, 1H), 3.91 (s, 2H), 3.62 (s, 2H), 3.22 (d, J=4.8 Hz, 2H), 2.97 (s, 2H), 2.58 (s, 2H), 1.44-1.27 (m, 13H), 0.88 (s, 6H).

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