Propynamide → 3-((2S,5R)-6-(benzyloxy)-7-oxo-1,6-diaza-bicyclo[3.2.1]octan-2-yl)isoxazole-5-carboxamide

HRID 515600

Reaction equation

HRID 515600 reaction equation
[C:1]([NH2:5])(=[O:4])[C:2]#[CH:3].[CH2:6]([O:13][N:14]1[C:20](=[O:21])[N:19]2[CH2:22][C@H:15]1[CH2:16][CH2:17][C@H:18]2/[C:23](/Cl)=[N:24]/[OH:25])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1>C(Cl)Cl.CCOC(C)=O>[CH2:6]([O:13][N:14]1[C:20](=[O:21])[N:19]2[CH2:22][C@H:15]1[CH2:16][CH2:17][C@H:18]2[C:23]1[CH:3]=[C:2]([C:1]([NH2:5])=[O:4])[O:25][N:24]=1)[C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1

Participants

5

Reactant 2

HCID 101445PropynamideHCID 89886626(2Z,2S,5R)-N-hydroxy-7-oxo-6-phenylmethoxy-1,6-diazabicyclo[3.2.1]octane-2-carboximidoyl chloride

Product 1

HCID 867013773-((2S,5R)-6-(benzyloxy)-7-oxo-1,6-diaza-bicyclo[3.2.1]octan-2-yl)isoxazole-5-carboxamideYield 32.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Propiolamide (0.30 g, 4.37 mmol) was added to a solution of (2S,5R,Z)-6-(benzyloxy)-N-hydroxy-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carb imido yl chloride (3.64 mmol) in dry DCM (10 mL), followed by the addition of TEA (0.56 mL, 4.0 mmol) in DCM (2 mL) over a 30 minute period. The reaction mixture was stirred at rt overnight. Then the mixture was diluted with EtOAc, washed with water and saturated sodium chloride. The combined organic layer was dried over Na2SO4, concentrated and purified by silica gel column chromatography (gradient elution 5:1 to 1:2, petroleum ether/EtOAc containing 1% TEA) to afford 3-((2S,5R)-6-(benzyloxy)-7-oxo-1,6-diaza-bicyclo[3.2.1]octan-2-yl)isoxazole-5-carboxamide (0.4 g, 32%) as a yellow solid. ESI-MS (EI+, m/z): 343 [M+H]+.

Workup

  1. washwashed with water and saturated sodium chloride
  2. dry with materialThe combined organic layer was dried over Na2SO4
  3. concentrationconcentrated
  4. custompurified by silica gel column chromatography (gradient elution 5:1 to 1:2, petroleum ether/EtOAc containing 1% TEA)

Sources & evidence

ORD record
ord-6ad301314de5489399e883b534ab5196
Source dataset
uspto-grants-2015_08
Patent number
US09108966B2

Linked notes

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