Acetic Acid → cis-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 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 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): 4.21-4.02 (m, 1H), 3.84-3.59 (m, 3H), 3.47-3.36 (m, 1H), 3.33 (dd, J=8.3, 4.4 Hz, 1H), 3.28-3.20 (m, 1H), 2.91-2.71 (m, 2H), 1.94-1.81 (m, 1H), 1.81-1.68 (m, 1H), 1.46 (s, 9H).

1. customAfter 16 hours the resulting mixture was removed from the 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-dfd1ecb716f0405ba9ecadc4c7f8eb25

Source dataset

uspto-grants-2014_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08680275B2