Triethylamine → (2S,5R)-6-Benzyloxy-N-[2-(dimethylamino)ethoxy]-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxamide

HRID 710992Notes

Reaction equation

HRID 710992 reaction equation
[CH2:1]([O:8][N:9]1[C:15](=[O:16])[N:14]2[CH2:17][C@H:10]1[CH2:11][CH2:12][C@H:13]2[C:18]([OH:20])=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.ClC(OCC(C)C)=O.C(N(CC)CC)C.Cl.Cl.[NH2:38][O:39][CH2:40][CH2:41][N:42]([CH3:44])[CH3:43]>C(Cl)Cl>[CH2:1]([O:8][N:9]1[C:15](=[O:16])[N:14]2[CH2:17][C@H:10]1[CH2:11][CH2:12][C@H:13]2[C:18]([NH:38][O:39][CH2:40][CH2:41][N:42]([CH3:44])[CH3:43])=[O:20])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 8471Triethylamine2×HCID 62365Isobutyl chloroformateHCID 10176354O-[2-(dimethylamino)ethyl]hydroxylamine dihydrochlorideHCID 57389355(2S,5R)-6-(Benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxylic acid

Product 1

HCID 72549871(2S,5R)-6-Benzyloxy-N-[2-(dimethylamino)ethoxy]-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxamideYield 40.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of the carboxylic acid (6b, 553 mg, 2.00 mmol) of Example 9 or 16 in dehydrated methylene chloride (10 mL) was cooled to 0° C. under an argon atmosphere, followed by adding dropwise isobutyl chloroformate (289 μL, 2.20 mmol). Then, triethylamine (293 μL) was added, followed by stirring for 30 minutes. Thereby, a mixed acid anhydride was prepared in the reaction system. To this reaction mixture were gradually added 2-(aminooxy)-N,N-dimethylethanamine dihydrochloride (591 mg) described in Reference Example 18 and triethylamine (930 μL) while washing with dehydrated methylene chloride (7.0 mL), followed by stirring at the same temperature for 1 hour. This reaction mixture was filtered though Kiriyama filter paper. Subsequently, the residue was washed with methanol and the filtrate was concentrated under reduced pressure. The resulting residue was dissolved in methylene chloride and water, and the organic layer extracted with methylene chloride was dried over magnesium sulfate, followed by distilling off under reduced pressure. The resulting residue was subjected to silica gel column chromatography (amino silica, chloroform/methanol=10/1) to afford 291.1 mg of the title compound as a colorless oil (yield 40%).

Workup

  1. washwhile washing with dehydrated methylene chloride (7.0 mL)
  2. stirringby stirring at the same temperature for 1 hour
  3. filtrationThis reaction mixture was filtered though Kiriyama
  4. filtrationfilter paper
  5. washSubsequently, the residue was washed with methanol
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. dissolutionThe resulting residue was dissolved in methylene chloride
  8. extractionwater, and the organic layer extracted with methylene chloride
  9. dry with materialwas dried over magnesium sulfate
  10. distillationby distilling off under reduced pressure

Sources & evidence

ORD record
ord-bf51a5a43cf04800b44ff8511caceab0
Source dataset
uspto-grants-2015_11
Patent number
US09181250B2

Reaction notes

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