Diisopropylethylamine → p-nitrobenzyl (1R,5S,6S)-2-[1-(4-carbamoyl-1,3-thiazol-2-yl)azetidin-3-yl]thio-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylate

HRID 891478ノート

反応式

HRID 891478 の反応式
C([S:4][CH:5]1[CH2:8][N:7]([C:9]2[S:10][CH:11]=[C:12]([C:14](=[O:16])[NH2:15])[N:13]=2)[CH2:6]1)(=O)C.C(O)(=O)C.NN.C1(P(O[C:38]2[C@H:39]([CH3:62])[C@H:40]3[C@@H:57]([C@H:58]([OH:60])[CH3:59])[C:56](=[O:61])[N:41]3[C:42]=2[C:43]([O:45][CH2:46][C:47]2[CH:52]=[CH:51][C:50]([N+:53]([O-:55])=[O:54])=[CH:49][CH:48]=2)=[O:44])(C2C=CC=CC=2)=O)C=CC=CC=1.C(N(C(C)C)CC)(C)C.C(=O)([O-])O.[Na+]>CN(C)C=O.C(#N)C.C(OCC)(=O)C>[C:14]([C:12]1[N:13]=[C:9]([N:7]2[CH2:8][CH:5]([S:4][C:38]3[C@H:39]([CH3:62])[C@@H:40]4[C@@H:57]([C@H:58]([OH:60])[CH3:59])[C:56](=[O:61])[N:41]4[C:42]=3[C:43]([O:45][CH2:46][C:47]3[CH:48]=[CH:49][C:50]([N+:53]([O-:55])=[O:54])=[CH:51][CH:52]=3)=[O:44])[CH2:6]2)[S:10][CH:11]=1)(=[O:16])[NH2:15]

参加物

9

反応物 5

HCID 81531DiisopropylethylamineHCID 165591Hydrazine, acetate (1:1)HCID 516892Sodium BicarbonateHCID 222428523-Acetylthio-1-(4-carbamoyl-1,3-thiazol-2-yl)azetidineHCID 131720384p-nitrobenzyl (1R,5S,6S)-2-(diphenylphosphoryloxy)-6-[(R)-1-hydroxyethyl)-1-methylcarbapen-2-em-3-carboxylate

生成物 1

HCID 131725295p-nitrobenzyl (1R,5S,6S)-2-[1-(4-carbamoyl-1,3-thiazol-2-yl)azetidin-3-yl]thio-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylate収率 106.2%

試薬・触媒・溶媒 3

HCID 6228Dimethylformamide溶媒HCID 6342Acetonitrile溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a solution of 3-acetylthio-1-(4-carbamoyl-1,3-thiazol-2-yl)azetidine (1.13 g, 4.39 mmol) (obtained as described in Reference Example 3) in dimethylformamide (57 ml) was added hydrazine acetate (485 mg, 5.27 mmol) at room temperature under an atmosphere of nitrogen and the mixture was stirred for 1 hour. After checking the completion of the reaction, a solution of p-nitrobenzyl (1R,5S,6S)-2-diphenylphosphoryloxy-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylate (2.61 g, 4.39 mmol) in acetonitrile (130 ml) was added dropwise to the resulting mixture in an ice bath under an atmosphere of nitrogen, followed by the addition of diisopropylethylamine (3.1 ml, 17.6 mmol). The mixture was stirred for 3 hours while gradually raising the temperature to room temperature. After checking the completion of the reaction, ethyl acetate and saturated aqueous sodium hydrogencarbonate solution were added to the reaction mixture. The resulting mixture was shaken in a separatory funnel and the ethyl acetate layer was separated, washed with 0.5 M aqueous sodium chloride solution, saturated aqueous sodium hydrogencarbonate solution and saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by chromatography on a silica gel column using methylene chloride-3% methanol, methylene chloride-6% methanol, methylene chloride-9% methanol and methylene chloride as the eluant to afford p-nitrobenzyl (1R,5S,6S)-2-[1-(4-carbamoyl-1,3-thiazol-2-yl)azetidin-3-yl]thio-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylate as a pale yellow solid (2.61 g, yield 94%).

後処理

  1. customthe completion of the reaction
  2. stirringThe mixture was stirred for 3 hours
  3. additionwere added to the reaction mixture
  4. stirringThe resulting mixture was shaken in a separatory funnel
  5. customthe ethyl acetate layer was separated
  6. washwashed with 0.5 M aqueous sodium chloride solution, saturated aqueous sodium hydrogencarbonate solution and saturated aqueous sodium chloride solution
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by chromatography on a silica gel column

出典と根拠

ORDレコード
ord-bfd04d3f77c04f70afe7d28fda0b996f
出典データセット
uspto-grants-2006_02
特許番号
US07001897B2

反応ノート

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