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Phosphoric Acid → (4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-3-[(2S,4S)-2-(4-methyl-2-oxoimidazolidin-1-yl)methylpyrrolidin-4-yl]thio-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid

HRID 1650868
ノート
印刷プレビュー

反応式

HRID 1650868 の反応式
[OH:1][C@@H:2]([C@H:4]1[C:10](=[O:11])[N:9]2[C@@H:5]1[C@@H:6]([CH3:45])[C:7]([S:18][C@@H:19]1[CH2:23][N:22](C(OCC3C=CC([N+]([O-])=O)=CC=3)=O)[C@H:21]([CH2:37][N:38]3[CH2:42][CH:41]([CH3:43])[NH:40][C:39]3=[O:44])[CH2:20]1)=[C:8]2[C:12]([O:14]CC=C)=[O:13])[CH3:3].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(OCC)(=O)CCCCC.[Na].P(=O)(O)(O)O.[H][H]>O1CCCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[OH-].[OH-].[Pd+2]>[OH:1][C@@H:2]([C@H:4]1[C:10](=[O:11])[N:9]2[C@@H:5]1[C@@H:6]([CH3:45])[C:7]([S:18][C@@H:19]1[CH2:23][NH:22][C@H:21]([CH2:37][N:38]3[CH2:42][CH:41]([CH3:43])[NH:40][C:39]3=[O:44])[CH2:20]1)=[C:8]2[C:12]([OH:14])=[O:13])[CH3:3]
参加物実験手順後処理出典と根拠反応ノート

参加物

9

反応物 5

HCID 1004Phosphoric AcidHCID 11776TriphenylphosphineHCID 53628222Sodium 2-ethyl hexanoateHCID 86743935allyl (4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-3-{(2S,4S)-2-(4-methyl-2-oxoimidazolidin-1-yl)methyl-1-(4-nitrobenzyloxycarbonyl)pyrrolidin-4-yl]thio-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylateHCID 178418361HCID 178418361、化合物

生成物 1

HCID 15056096
(4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-3-[(2S,4S)-2-(4-methyl-2-oxoimidazolidin-1-yl)methylpyrrolidin-4-yl]thio-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid
収率 17.9%

試薬・触媒・溶媒 3

HCID 9942167Palladium hydroxide触媒HCID 178418397HCID 178418397、化合物触媒HCID 8028Tetrahydrofuran溶媒2 回

実験手順

To a solution of allyl (4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-3-{(2S,4S)-2-(4-methyl-2-oxoimidazolidin-1-yl)methyl-1-(4-nitrobenzyloxycarbonyl)pyrrolidin-4-yl]thio-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (2.45 g) in tetrahydrofuran (50 ml) were added triphenylphosphine (0.50 g), sodium 2-ethyl hexanoate (0.70 g) and tetrakis(triphenylphosphine)palladium(0) (0.22 g) successively with stirring at ambient temperature. After stirring at the same temperature for 1 hour, the reaction mixture was evaporated in vacuo to give a residue. A mixture of the residue, 20% palladium hydroxide on carbon (0.5 g), 0.1M phosphoric acid buffer (pH=6.0, 80 ml) and tetrahydrofuran (80 ml) was stirred for 5 hours under atmospheric pressure of hydrogen at ambient temperature. After the catalyst was filtered off, the filtrate was evaporated in vacuo to remove the organic solvent. The residue was chromatographed on nonionic adsorption resin, "Diaion HP-20" (trademark, made by Mitsubishi Chemical Industries) (30 ml) eluting in turn with water (90 ml) and 5% aqueous acetone (100 ml). The fractions containing the desired compound were collected and lyophilized to give (4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-3-[(2S,4S)-2-(4-methyl-2-oxoimidazolidin-1-yl)methylpyrrolidin-4-yl]thio-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid (0.29 g).

後処理

  1. stirringAfter stirring at the same temperature for 1 hour
  2. customthe reaction mixture was evaporated in vacuo
  3. customto give a residue
  4. filtrationAfter the catalyst was filtered off
  5. customthe filtrate was evaporated in vacuo
  6. customto remove the organic solvent
  7. customThe residue was chromatographed on nonionic adsorption resin, "Diaion
  8. wash" (trademark, made by Mitsubishi Chemical Industries) (30 ml) eluting in turn with water (90 ml) and 5% aqueous acetone (100 ml)
  9. additionThe fractions containing the desired compound
  10. customwere collected

出典と根拠

ORDレコード
ord-64e077e4d7084016b5685ffc1afd5b4d
出典データセット
uspto-grants-1990_05
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US04925838

反応ノート

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