Ammonia → Avibactam Impurity 19

HRID 575883노트

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HRID 575883 반응식
[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.C([N:23](CC)CC)C.ClC(OCC(C)C)=O.N>ClCCl.CCCCCC.C(OCC)(=O)C.O>[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]([NH2:23])=[O:20])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

참가 물질

8

반응물 4

HCID 222AmmoniaHCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 66870454(2R,5S)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxylic acid

생성물 1

HCID 66870463Avibactam Impurity 19수율 87.3%

시약·촉매·용매 3

HCID 962Water용매HCID 6344Dichloromethane용매HCID 21226206Ethyl acetate hexane용매

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온도
0 °C

실험 절차

230 mg (0.84 mmol) of (2R,5S)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxylic acid was dissolved in dehydrated dichloromethane (4.2 mL), and 110 mg of triethylamine was added, followed by cooling to 0° C. 137 mg of isobutyl chloroformate was added to the mixture, followed by stirring at the same temperature for 20 minutes. 0.6 mL of aqueous ammonia was added to the reaction mixture, followed by stirring at room temperature for 1 hour. Subsequently, water (10 mL) was added and the organic layer was aliquoted, followed by sequential washing with water and saturated brine and drying over anhydrous magnesium sulfate. The residue resulting from concentration of the solvent under reduced pressure was applied to silica gel column chromatography (hexane/ethyl acetate=1/3), and subsequently crystallized with chloroform/hexane=1:3 to afford 202 mg of the title compound as a colorless crystalline powder (yield 87%). Enantiomeric excess: 99.9% ee or more (CHIRALPAK AD-H, 4.6×150 mm, hexane/ethanol=4/1, UV 210 nm, flow rate 1 mL/min., retention time 10.3 min.).

후처리

  1. stirringby stirring at room temperature for 1 hour
  2. washby sequential washing with water and saturated brine
  3. dry with materialdrying over anhydrous magnesium sulfate
  4. customThe residue resulting from concentration of the solvent under reduced pressure
  5. customsubsequently crystallized with chloroform/hexane=1:3

출처 및 근거

ORD 기록
ord-101be8caca0741b2a1b77586dafaea0c
출처 데이터셋
uspto-grants-2015_05
특허 번호
US09035062B2

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