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

HRID 925135Notes

Reaction equation

HRID 925135 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 95.1%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6342AcetonitrileSolvent

Procedure

To a solution of 4.14 g (13.51 mmol) of (2S,5R)-tert-butyl 5-(benzyloxyamino)piperidine-2-carboxylate in dehydrated acetonitrile (615 mL), under argon atmosphere, at 0° C., was added triethylamine 4.9 mL (35.16 mmol), and subsequently 1.18 mL (9.78 mmol) of diphosgene was added dropwise within 5 minutes, followed by stirring at the same temperature for 10 minutes. 182 mg (1.623 mmol) of 4-dimethylaminopyridine was added to this solution, and the temperature was raised to room temperature, followed by allowing to react for 3 hours. After the reaction mixture was concentrated under reduced pressure to the volume of one tenth thereof, the resulting concentrated solution was diluted with ethyl acetate, washed sequentially with water, 5% aqueous citric acid solution, 6.5% aqueous sodium hydrogencarbonate solution and saturated brine and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The resulting residue was applied 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, and the generated precipitate was filtered off. The wet crystal was washed with hexane, and subsequently dried under reduced pressure at room temperature to afford the title compound 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. additionwas added dropwise within 5 minutes
  2. customto react for 3 hours
  3. concentrationAfter the reaction mixture was concentrated under reduced pressure to the volume of one tenth
  4. additionthe resulting concentrated solution was diluted with ethyl acetate
  5. washwashed sequentially with water, 5% aqueous citric acid solution, 6.5% aqueous sodium hydrogencarbonate solution and saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. distillationthe solvent was distilled off under reduced pressure

Sources & evidence

ORD record
ord-98e4830795764f9cafc7f34c0be3953e
Source dataset
uspto-grants-2016_03
Patent number
US09284273B2

Reaction notes

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