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

Temperature

20 °C

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)+.

1. customThe ice-bath was removed
2. temperatureThe solution was cooled to 0° C.
3. addition10 mL EtOAc and 10 mL H2O were added
4. customThe layers were separated
5. extractionthe aqueous layer was extracted with 10 mL EtOAc
6. washThe combined organic layers were washed with 5 mL H2O
7. dry with materialwere dried over anhydrous Na2SO4
8. filtrationThe mixture was filtered
9. concentrationthe filtrate was concentrated
10. custompurified via flash column chromatography
11. customto give

ORD record

ord-10d5ac13c1874076adca96732601870c

Source dataset

uspto-grants-2008_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07399765B2