Ammonia → Avibactam Impurity 19

HRID 1620463ノート

反応式

HRID 1620463 の反応式
[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

参加物

8

反応物 4

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

生成物 1

HCID 66870463Avibactam Impurity 19収率 87.3%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6344Dichloromethane溶媒HCID 21226206Ethyl acetate hexane溶媒

反応条件

温度
0 °C

実験手順

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.).

後処理

  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

出典と根拠

ORDレコード
ord-422032128f5f4cf781dce35c59c1f5c4
出典データセット
uspto-grants-2014_07
特許番号
US08772490B2

反応ノート

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