1-Azabicyclo[3.2.0]heptane-2-carboxylic acid, 6-[(1R)-1-hydroxyethyl]-4-methyl-3,7-dioxo-, (4-nitrophenyl)methyl ester, (4R,5R,6S)- → 4-Nitrobenzyl (1R,5S,6S)-2-((2S,4S)-2-[3-(4-nitrobenzyloxycarbonylamino)azetidin-1-ylcarbonyl]-1-(4-nitrobenzyloxycarbonyl)pyrrolidin-4-ylthio)-6-[(1R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylate

HRID 727710ノート

反応式

HRID 727710 の反応式
C1([ClH]P([ClH]C2C=CC=CC=2)(Cl)=O)C=CC=CC=1.[OH:18][C@@H:19]([C@H:21]1[C:42](=[O:43])[N:23]2[CH:24]([C:29]([O:31][CH2:32][C:33]3[CH:38]=[CH:37][C:36]([N+:39]([O-:41])=[O:40])=[CH:35][CH:34]=3)=[O:30])[C:25](=O)[C@H:26]([CH3:27])[C@H:22]12)[CH3:20].[SH:44][C@@H:45]1[CH2:49][N:48]([C:50]([O:52][CH2:53][C:54]2[CH:59]=[CH:58][C:57]([N+:60]([O-:62])=[O:61])=[CH:56][CH:55]=2)=[O:51])[C@H:47]([C:63]([N:65]2[CH2:68][CH:67]([NH:69][C:70]([O:72][CH2:73][C:74]3[CH:79]=[CH:78][C:77]([N+:80]([O-:82])=[O:81])=[CH:76][CH:75]=3)=[O:71])[CH2:66]2)=[O:64])[CH2:46]1>C(#N)C.C(OCC)(=O)C>[N+:80]([C:77]1[CH:76]=[CH:75][C:74]([CH2:73][O:72][C:70]([NH:69][CH:67]2[CH2:66][N:65]([C:63]([C@@H:47]3[CH2:46][C@H:45]([S:44][C:25]4[C@H:26]([CH3:27])[C@@H:22]5[C@@H:21]([C@H:19]([OH:18])[CH3:20])[C:42](=[O:43])[N:23]5[C:24]=4[C:29]([O:31][CH2:32][C:33]4[CH:34]=[CH:35][C:36]([N+:39]([O-:41])=[O:40])=[CH:37][CH:38]=4)=[O:30])[CH2:49][N:48]3[C:50]([O:52][CH2:53][C:54]3[CH:59]=[CH:58][C:57]([N+:60]([O-:62])=[O:61])=[CH:56][CH:55]=3)=[O:51])=[O:64])[CH2:68]2)=[O:71])=[CH:79][CH:78]=1)([O-:82])=[O:81]

参加物

5

反応物 2

HCID 98853021-Azabicyclo[3.2.0]heptane-2-carboxylic acid, 6-[(1R)-1-hydroxyethyl]-4-methyl-3,7-dioxo-, (4-nitrophenyl)methyl ester, (4R,5R,6S)-HCID 10929753(2S, 4S)-4-Mercapto-2-[3-(4-nitrobenzyloxycarbonylamino)azetidin-1-ylcarbonyl]-1-(4-nitrobenzyloxycarbonyl)pyrrolidine

生成物 1

HCID 109750254-Nitrobenzyl (1R,5S,6S)-2-((2S,4S)-2-[3-(4-nitrobenzyloxycarbonylamino)azetidin-1-ylcarbonyl]-1-(4-nitrobenzyloxycarbonyl)pyrrolidin-4-ylthio)-6-[(1R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylate収率 32.3%

試薬・触媒・溶媒 2

HCID 6342Acetonitrile溶媒2 回HCID 8857Ethyl Acetate溶媒

実験手順

167 μl of diphenylphosphoric acid chloride and 140 μl of ditsopropylethylamine were added dropwise at the same time, whilst ice-cooling, to a solution of 278 mg of 4-nitrobenzyl (1R,5R,6S)-6-[(1R)-1-hydroxyethyl]-1-methyl-2-oxo-1-carbapenam-3-carboxylate in 4 ml of dry acetonitrile, and the resulting mixture was stirred at the same temperature for 1 hour. At the end of this time, a solution of 430 mg of (2S,4S)-4-mercapto-2-[3-(4-nitrobenzyloxycarbonylamino)azetidin-1-ylcarbonyl]-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (prepared as described in Preparation 113) in 4 ml of dry acetonitrile and 134 μl of ditsopropylethylamine were added dropwise at the same time to the mixture, whilst ice-cooling. The resulting mixture was then stirred at the same temperature for 2 hours, after which it was left to stand overnight whilst ice-cooling. The reaction mixture was then diluted with ethyl acetate and washed with water and with an aqueous solution of sodium chloride. The ethyl acetate layer was dehydrated over anhydrous magnesium sulfate and then concentrated by evaporation under reduced pressure. The resulting residue was subjected to silica gel column chromatography, and the fractions obtained by elution with a 98:2 by volume mixture of ethyl acetate and methanol were combined and concentrated by evaporation under reduced pressure, to give 224 mg of the title compound, as a powder.

後処理

  1. temperaturecooling
  2. stirringThe resulting mixture was then stirred at the same temperature for 2 hours
  3. waitafter which it was left
  4. waitto stand overnight
  5. temperaturewhilst ice-cooling
  6. washwashed with water and with an aqueous solution of sodium chloride
  7. concentrationconcentrated by evaporation under reduced pressure
  8. customthe fractions obtained by elution with a 98:2 by volume mixture of ethyl acetate and methanol
  9. concentrationconcentrated by evaporation under reduced pressure

出典と根拠

ORDレコード
ord-12bc87c7ff7b447d98e043ef2f2dea00
出典データセット
uspto-grants-1998_01
特許番号
US05712267

反応ノート

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