Diisopropylethylamine → Ethyl (2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxylate

HRID 2272850Notes

Reaction equation

Cl[C:2](Cl)([O:4]C(=O)OC(Cl)(Cl)Cl)Cl.[CH2:13]([O:20][NH:21][C@H:22]1[CH2:27][NH:26][C@H:25]([C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH2:24][CH2:23]1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.CCN(C(C)C)C(C)C>C(Cl)Cl>[CH2:13]([O:20][N:21]1[C:2](=[O:4])[N:26]2[CH2:27][C@H:22]1[CH2:23][CH2:24][C@H:25]2[C:28]([O:30][CH2:31][CH3:32])=[O:29])[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1

Participants

Conditions

Temperature: 20 °C

Procedure

Triphosgene (21.3 g, 72 mmol) was added in portions to a solution of (2S,5R)-ethyl 5-((benzyloxy)amino)piperidine-2-carboxylate (50 g, 0.18 mol) and DIPEA (128 mL, 0.72 mol) in DCM (2000 mL) at 0° C. After stirring at 20° C. overnight, the reaction mixture was washed with H3PO4 (10%), sat. NaHCO3 and saturated NaCl. The combined organic layer was concentrated under reduced pressure and purified by silica gel column chromatography (3:1 petroleum ether/EtOAc) to afford (2S,5R)-ethyl 6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxylate (27.4 g, 50%) as a yellow solid. 1H NMR (400 Mz, CDCl3): δ 7.43-7.36 (m, 5H), 5.06 (d, J=11.4 Hz, 1H), 4.90 (d, J=11.4 Hz, 1H), 4.24 (q, J=7.1 Hz, 2H), 4.11-4.08 (m, 1H), 3.32-3.31 (m, 1H), 3.08-3.05 (m, 1H), 2.93 (d, J=11.9 Hz, 1H), 2.14-2.05 (m, 2H), 2.05-2.00 (m, 1H), 1.71-1.63 (m, 1H), 1.29 (t, J=7.1 Hz, 3H).

Workup

washthe reaction mixture was washed with H3PO4 (10%), sat. NaHCO3 and saturated NaCl
concentrationThe combined organic layer was concentrated under reduced pressure
custompurified by silica gel column chromatography (3:1 petroleum ether/EtOAc)

Sources & evidence

ORD record: ord-0da5f3d6971644638e0f43f88b5018e3
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09120795B2

Reaction notes

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