Benzylamine → Tert-butyl 3-benzyl-3,6-diazabicyclo[3.2.1]octane-6-carboxylate

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Reaction Conditions

Reaction Steps

To a solution of the crude product of Example 2B (2.92 mmol) in CH3OH at 0° C. was added benzylamine (0.35 mL, 3.21 mmol) and NaCNBH3 (1.83 g, 29.2 mmol). The ice-bath was removed and the mixture stirred at 20° C. for 24 h. The solution was cooled to 0° C. and 10 mL EtOAc and 10 mL H2O were added followed by 5 mL of saturated, aqueous NaHCO3. The layers were separated and the aqueous layer was extracted with 10 mL EtOAc. The combined organic layers were washed with 5 mL H2O followed by 5 mL brine, then were dried over anhydrous Na2SO4. The mixture was filtered and the filtrate was concentrated and purified via flash column chromatography to give 0.68 g (2.25 mmol, 77% two-step yield) of the title compound. 1H NMR (CH3OH-d4, 300 MHz) δ 1.37 and 1.51 (s, rotamers, 9H), 1.46 (m, 1H), 1.57 (dd, J=11.2, 7.46 Hz, 1H), 1.88 (m, 1H), 1.97 (m, 1H), 2.32 (m, 2H), 2.82 (m, 1H), 3.02 (m, 1H), 3.52 (m, 3H), 3.91 (m, 1H), 7.20 (m, 1H), 7.27 (m, 4H); MS (DCl/NH3) m/z 303 (M+H)+.

Provenance & Evidence