Yield: 90%

Reaction Conditions:

with 10 wt% Pd(OH)2 on carbon;hydrogen in ethyl acetate at 25; under 5171.62 Torr;

Steps:

20.1 Step 1 : tert-butyl 8-oxo-3-azabicyclo[3.2.1]octane-3-carboxylate
Di-tert-butyl dicarbonate (5.81 g, 26.6 mmol) and Pearlman's catalyst (1.55 g, 23.2 mmol) were successively added to a solution of 3-benzyl-3-azabicyclo[3.2.1]octan-8-one obtained from commercial sources (Reference Mityuk, et al, Synthesis, 2010, 493-97, CAS 83507-33-9) (5.0 g, 22.0 mmol) in EtOAc (74 mL) at 25 °C. The reaction vessel was alternately filled with nitrogen and evacuated (3x) and then filled and evacuated with hydrogen (2x). The mixture was stirred overnight under 100 psi of H₂. The mixture was filtered through a pad of Celite which was washed with ethyl acetate. The filtrate was concentrated and the crude product was purified by silica gel chromatography (heptane: EtOAc, 0: 100-100:0) to provide the title compound (4.49 g, 90%) as a solid. LC/MS [M-Me] = 21 1.1 ; ¹H NMR (400 MHz, CDCI₃) δ 4.38 (d, J=14.0 Hz, 1 H), 4.20 (d, J=14.0 Hz, 1 H), 3.27 (d, J=13.3 Hz, 1 H), 3.17 (d, J=13.3 Hz, 1 H), 2.24 (d, J=15.6 Hz, 2H), 1.76-1.99 (m, 4H), 1.49 (s, 9H).

References:

PFIZER INC.;SCHNUTE, Mark Edward;FLICK, Andrew Christopher;JONES, Peter;KAILA, Neelu;MENTE, Scot Richard;TRZUPEK, John David;VAZQUEZ, Michael L.;XING, Li;ZHANG, Liying;WENNERSTAL, Goran Mattias;ZAMARATSKI, Edouard WO2016/120849, 2016, A1 Location in patent:Page/Page column 63