Acetic Acid → (1S,6R)-3-Boc-3,8-diazabicyclo[4.2.0]octane

To a solution of (1R,6S)-tert-butyl 8-((S)-1-phenylethyl)-3,8-diazabicyclo[4.2.0]octane-3-carboxylate (1.5 g, 75%) in EtOH (50 mL) was added AcOH (1.5 mL). The resulting mixture was cycled through an ThalesNano H-Cube containing a 20% Pd(OH)2/C catalyst cartridge at 50° C. and 100 bar of hydrogen pressure. After 16 hours the resulting mixture was removed from the ThalesNano H-Cube and poured over a saturated sodium carbonate solution (100 mL). The aqueous layer was extracted with DCM (50 mL) four times. The organic layers were combined, dried over Na2SO4, filtered and concentrated under reduced pressure to yield the title compound (755 mg, 75%) which was used in the next step without purification. MS (ESI) mass calcd. for C11H20N2O2, 212.2; m/z found, 213.1 [M+H]+. 1H NMR (500 MHz, CDCl3): 4.18-4.00 (m, 1H), 3.85-3.57 (m, 3H), 3.44-3.34 (m, 1H), 3.28 (dt, J=13.1, 6.5 Hz, 1H), 3.24-3.13 (m, 1H), 2.82-2.72 (m, 1H), 1.93-1.83 (m, 1H), 1.82-1.70 (m, 1H), 1.48 (s, 9H).

1. customAfter 16 hours the resulting mixture was removed from the ThalesNano H-Cube
2. additionpoured over a saturated sodium carbonate solution (100 mL)
3. extractionThe aqueous layer was extracted with DCM (50 mL) four times
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure

ORD record

ord-b89ac1053c1e4e329e3e999530e3c841

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09062044B2