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

HRID 710961Notes

Reaction equation

HRID 710961 reaction equation
[CH2:1]([O:8][NH:9][C@H:10]1[CH2:15][NH:14][C@H:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.[O:30]=[C:31](Cl)OC(Cl)(Cl)Cl>C(#N)C.CN(C)C1C=CN=CC=1>[CH2:1]([O:8][N:9]1[C:31](=[O:30])[N:14]2[CH2:15][C@H:10]1[CH2:11][CH2:12][C@H:13]2[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 10426DiphosgeneHCID 57389512(2S,5R)-tert-butyl 5-(benzyloxyamino)piperidine-2-carboxylate

Product 1

HCID 57389353(2S,5R)-tert-butyl 6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxylateYield 69%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6342AcetonitrileSolvent

Procedure

To a solution of (2S,5R)-tert-butyl 5-(benzyloxyamino)piperidine-2-carboxylate (4.14 g, 13.51 mmol) in dehydrated acetonitrile (615 mL) was added triethylamine (4.9 mL) under an argon atmosphere at 0° C., followed by adding dropwise diphosgene (1.18 mL) for 5 minutes, and stirring at the same temperature for 10 minutes. To this solution was added 4-dimethylaminopyridine (182 mg), followed by raising the temperature to room temperature and allowing to react for 3 hours. The reaction mixture was concentrated under reduced pressure to the volume of one tenth thereof, the resulting concentrated solution was diluted with ethyl acetate, followed by washing with water, 5% citric acid aqueous solution, 6.5% sodium bicarbonate aqueous solution, and saturated brine sequentially, then drying over anhydrous magnesium sulfate, and distilling off the solvent under reduced pressure. The resulting residue was subjected to silica gel column chromatography (hexane/ethyl acetate=2/1) to afford 3.09 g of the title compound (yield 69%). The resulting solid was recrystallized from ethyl acetate-hexane, the generated precipitate was filtered off. The wet crystal was washed with hexane, followed by drying at room temperature under reduced pressure, and the title compound was afforded as a colorless crystalline powder. Enantiomeric excess 99.4% ee (CHIRALPAK AD-H, 4.6×150 mm, hexane/ethanol=2/1, UV 210 nm, flow rate 1 mL/min., retention time 8.0 min.).

Workup

  1. customto react for 3 hours
  2. concentrationThe reaction mixture was concentrated under reduced pressure to the volume of one tenth
  3. additionthe resulting concentrated solution was diluted with ethyl acetate
  4. washby washing with water, 5% citric acid aqueous solution, 6.5% sodium bicarbonate aqueous solution, and saturated brine sequentially
  5. dry with materialdrying over anhydrous magnesium sulfate
  6. distillationdistilling off the solvent under reduced pressure

Sources & evidence

ORD record
ord-9d8911c7952447babed37015395e0ce3
Source dataset
uspto-grants-2015_11
Patent number
US09181250B2

Reaction notes

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