(2S,4S)-4-(4-methoxybenzyl)thio-1-(4-nitrobenzyloxycarbonyl)-L-proline → (2S,4S)-4-(4-Methoxybenzylthio)-2-{4-[2-(4-nitrobenzyloxycarbonyl)oxyethyl]-1-homopiperazinylcarbonyl}-1-(4-nitrobenzyloxycarbonyl)pyrrolidine

HRID 37347ノート

反応式

HRID 37347 の反応式
[CH3:1][O:2][C:3]1[CH:31]=[CH:30][C:6]([CH2:7][S:8][C@@H:9]2[CH2:13][N:12]([C:14]([O:16][CH2:17][C:18]3[CH:23]=[CH:22][C:21]([N+:24]([O-:26])=[O:25])=[CH:20][CH:19]=3)=[O:15])[C@H:11]([C:27](O)=[O:28])[CH2:10]2)=[CH:5][CH:4]=1.FC(F)(F)C(O)=O.FC(F)(F)C(O)=O.[N+:46]([C:49]1[CH:68]=[CH:67][C:52]([CH2:53][O:54][C:55]([O:57][CH2:58][CH2:59][N:60]2[CH2:66][CH2:65][CH2:64][NH:63][CH2:62][CH2:61]2)=[O:56])=[CH:51][CH:50]=1)([O-:48])=[O:47]>C(#N)C.C(N(C(C)C)CC)(C)C.C(OCC)(=O)C>[CH3:1][O:2][C:3]1[CH:31]=[CH:30][C:6]([CH2:7][S:8][C@@H:9]2[CH2:13][N:12]([C:14]([O:16][CH2:17][C:18]3[CH:23]=[CH:22][C:21]([N+:24]([O-:26])=[O:25])=[CH:20][CH:19]=3)=[O:15])[C@H:11]([C:27]([N:63]3[CH2:64][CH2:65][CH2:66][N:60]([CH2:59][CH2:58][O:57][C:55]([O:54][CH2:53][C:52]4[CH:67]=[CH:68][C:49]([N+:46]([O-:48])=[O:47])=[CH:50][CH:51]=4)=[O:56])[CH2:61][CH2:62]3)=[O:28])[CH2:10]2)=[CH:5][CH:4]=1

参加物

6

反応物 2

HCID 15297071(2S,4S)-4-(4-methoxybenzyl)thio-1-(4-nitrobenzyloxycarbonyl)-L-prolineHCID 867486964-[2-(4-Nitrobenzyloxycarbonyl)oxyethyl]homopiperazine bis(trifluoroacetate)

生成物 1

HCID 10580921(2S,4S)-4-(4-Methoxybenzylthio)-2-{4-[2-(4-nitrobenzyloxycarbonyl)oxyethyl]-1-homopiperazinylcarbonyl}-1-(4-nitrobenzyloxycarbonyl)pyrrolidine収率 62.1%

試薬・触媒・溶媒 3

HCID 6342Acetonitrile溶媒2 回HCID 8857Ethyl Acetate溶媒HCID 81531Diisopropylethylamine溶媒

実験手順

860 mg of (2S,4S)-4-(4-methoxybenzylthio)-1-(4-nitrobenzyloxycarbonyl)-2-pyrrolidinecarboxylic acid [prepared as described in Preparation 1(b)] were dissolved in 8 ml of anhydrous acetonitrile, and 410 mg of N,N'-carbonyldiimidazole were added to the resulting solution. The resulting mixture was then stirred at room temperature for 30 minutes, after which a solution of 1250 mg of 4-[2-(4-nitrobenzyloxycarbonyl)oxyethyl]homopiperazine bis(trifluoroacetate) in 5 ml of acetonitrile and 860 μl of diisopropylethylamine were added, in that order. The resulting mixture was then stirred at room temperature for 35 hours. At the end of this time, the reaction mixture was diluted with 100 ml of ethyl acetate and washed with an aqueous solution of sodium hydrogencarbonate and with an aqueous solution of sodium chloride, in that order. The organic layer was then dried over anhydrous sodium sulfate and concentrated by evaporation under reduced pressure. The residue was subjected to column chromatography through silica gel using mixtures of ethyl acetate and methanol ranging from 98:2 to 95:5 by volume as the eluent. Those fractions containing the title compound were collected and concentrated by evaporation under reduced pressure, to afford 900 mg of the title compound.

後処理

  1. stirringThe resulting mixture was then stirred at room temperature for 35 hours
  2. washwashed with an aqueous solution of sodium hydrogencarbonate and with an aqueous solution of sodium chloride, in that order
  3. dry with materialThe organic layer was then dried over anhydrous sodium sulfate
  4. concentrationconcentrated by evaporation under reduced pressure
  5. additionThose fractions containing the title compound
  6. customwere collected
  7. concentrationconcentrated by evaporation under reduced pressure

出典と根拠

ORDレコード
ord-a097453ddb5640d6ab3aab6c3c8eff05
出典データセット
uspto-grants-1995_05
特許番号
US05420119

反応ノート

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