Hydrogen Peroxide → (2S,4S)-4-azido-4-[(2S,4S)-5-oxo-4-propan-2-yloxolan-2-yl]-2-propan-2-ylbutanoic acid

HRID 264921

反応式

HRID 264921 の反応式
OO.[OH-].[Li+].[CH:5]([C@@H:8]1[CH2:12][C@@H:11]([C@@H:13]([N:34]=[N+:35]=[N-:36])[CH2:14][C@H:15]([C:19](N2[C@@H](CC3C=CC=CC=3)COC2=O)=[O:20])[CH:16]([CH3:18])[CH3:17])[O:10][C:9]1=[O:37])([CH3:7])[CH3:6].S([O-])([O-])=[O:39].[Na+].[Na+].C1(C)C=CC(S(O)(=O)=O)=CC=1>O1CCCC1.C1(C)C=CC=CC=1.O>[CH:5]([C@@H:8]1[CH2:12][C@@H:11]([C@@H:13]([N:34]=[N+:35]=[N-:36])[CH2:14][C@H:15]([C:19]([OH:20])=[O:39])[CH:16]([CH3:17])[CH3:18])[O:10][C:9]1=[O:37])([CH3:6])[CH3:7]

参加物

9

反応物 5

HCID 784Hydrogen PeroxideHCID 3939Lithium HydroxideHCID 6101p-Toluenesulfonic acidHCID 24437Sodium SulfiteHCID 533855072-Oxazolidinone, 3-[(2S,4S)-4-azido-2-(1-methylethyl)-1-oxo-4-[(2S,4S)-tetrahydro-4-(1-methylethyl)-5-oxo-2-furanyl]butyl]-4-(phenylmethyl)-, (4S)-

生成物 1

HCID 53970123(2S,4S)-4-azido-4-[(2S,4S)-5-oxo-4-propan-2-yloxolan-2-yl]-2-propan-2-ylbutanoic acid

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 1140Toluene溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
5 °C

実験手順

175 ml of water, 74 ml of 30% hydrogen peroxide solution and 5.9 g of lithium hydroxide are slowly added in succession to a solution, stirred at -5° C., of 55.3 g of 3(S)-isopropyl-5(S)-{1(S)-azido-4-methyl-3(S)-[(4(S)-benzyl-oxazolidin-2-on-3-yl)-carbonyl]-pentyl}-tetrahydrofuran-2-one in 500 ml of tetrahydrofuran. The reaction mixture is stirred for one hour at 5° C. and for 150 minutes at room temperature, and then 750 ml of aqueous 1M sodium sulfite solution are added at 3° C. over a period of 30 minutes and the mixture is stirred for a further 30 minutes at room temperature. The reaction mixture is then freed of tetrahydrofuran by concentration, and the aqueous solution is washed three times with 1200 ml of ethyl acetate, the organic phases being back-extracted three times with 100 ml of 0.1N sodium hydroxide. The combined aqueous phases are adjusted to pH 1-2 with approximately 200 ml of 4N hydrochloric acid and are extracted with 3×1200 ml of ethyl acetate. The organic phases are combined, dried over magnesium sulfate and concentrated by evaporation, yielding the crude product which, for the purpose of cyclisation of the opened lactone, is dissolved in 500 ml of toluene and stirred for 2 hours at 50° C. with approximately 1 g of molecular sieve and approximately 1 g of p-toluenesulfonic acid. Filtration, concentration by evaporation and purification of the residue by means of FC (hexane/ethyl acetate/glacial acetic acid=30:60:1) yield the title compound, which crystallises spontaneously: m.p.=56°-58° C.; Rf (hexane/ethyl acetate/glacial acetic acid =30:60:1)=0.62; HPLC Rt =14.46 minutes; FAB-MS (M+H)+ =298.

後処理

  1. stirringthe mixture is stirred for a further 30 minutes at room temperature
  2. concentrationThe reaction mixture is then freed of tetrahydrofuran by concentration
  3. washthe aqueous solution is washed three times with 1200 ml of ethyl acetate
  4. extractionthe organic phases being back-extracted three times with 100 ml of 0.1N sodium hydroxide
  5. extractionare extracted with 3×1200 ml of ethyl acetate
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated by evaporation
  8. customyielding the crude product which
  9. filtrationFiltration, concentration
  10. customby evaporation and purification of the residue by means of FC (hexane/ethyl acetate/glacial acetic acid=30:60:1)

出典と根拠

ORDレコード
ord-695f33a7df314fcd88871c9ce42407c7
出典データセット
uspto-grants-1997_07
特許番号
US05646143

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