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

HRID 1424512Notes

Reaction equation

HRID 1424512 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

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 86675005Ethyl (2S,5R)-5-((benzyloxy)amino)piperidine-2-carboxylate

Product 1

HCID 72204974Ethyl (2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxylateYield 125%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Triphosgene (21.3 g, 72 mmol) was added in portions to a 0° C. 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). The reaction mixture was allowed to warm to rt. After stirring at rt 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

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

Sources & evidence

ORD record
ord-616b20c3b9b5491cbfd54868143c0e42
Source dataset
uspto-grants-2015_01
Patent number
US08927724B2

Reaction notes

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