Hydrochloric Acid → (3R,5R,6R)-6-amino-3-(p-nitrobenzyloxycarbonyl)-7-oxo-3-(2-oxo-3-ureidoimidazolidin-1-yl)-4-thia-1-azabicyclo[3.2.0]heptane

HRID 2081736ノート

反応式

HRID 2081736 の反応式
[NH2:1][C@@H:2]1[C:8](=[O:9])[N:7]2[C@@H:3]1[S:4][C@@:5]([N:23]1[CH2:27][CH2:26][N:25]([NH2:28])[C:24]1=[O:29])([C:10]([O:12][CH2:13][C:14]1[CH:19]=[CH:18][C:17]([N+:20]([O-:22])=[O:21])=[CH:16][CH:15]=1)=[O:11])[CH2:6]2.Cl.[O-:31][C:32]#[N:33].[Na+].C(=O)([O-])O.[Na+]>O.CO>[NH2:1][C@@H:2]1[C:8](=[O:9])[N:7]2[C@@H:3]1[S:4][C@:5]([C:10]([O:12][CH2:13][C:14]1[CH:15]=[CH:16][C:17]([N+:20]([O-:22])=[O:21])=[CH:18][CH:19]=1)=[O:11])([N:23]1[CH2:27][CH2:26][N:25]([NH:28][C:32]([NH2:33])=[O:31])[C:24]1=[O:29])[CH2:6]2

参加物

7

反応物 4

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 517096Sodium CyanateHCID 53724867(3R,5R,6R)-6-amino-3-(3-amino-2-oxoimidazolidin-1-yl)-3-(p-nitrobenzyloxycarbonyl)-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane

生成物 1

HCID 54470742(3R,5R,6R)-6-amino-3-(p-nitrobenzyloxycarbonyl)-7-oxo-3-(2-oxo-3-ureidoimidazolidin-1-yl)-4-thia-1-azabicyclo[3.2.0]heptane収率 77.9%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 962Water溶媒2 回

実験手順

In a mixed solvent consisting of 30 ml of water and 30 ml of methanol was suspended 5.00 g of (3R,5R,6R)-6-amino-3-(3-amino-2-oxoimidazolidin-1-yl)-3-(p-nitrobenzyloxycarbonyl)-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane. To suspension was added 2.96 ml of concentrated hydrochloric acid with water cooling. To the resulting solution was added 1.36 g of sodium cyanate in 10 minutes, and the mixture was stirred at room temperature for 30 minutes. The reaction mixture was filtered. To the filtrate were added 50 ml of ethyl acetate and 50 ml of water. The aqueous layer was separated. The organic layer was extracted three times each with 30 ml of water. The extracts were combined with the aqueous layer obtained previously. The combined aqueous solution was adjusted to pH 6.9 with sodium hydrogencarbonate. The solvent was removed by distillation under reduced pressure. The residue was dehydrated by four times of azeotropy with ethanol. To the resulting residue was added a mixed solvent consisting of 50 ml of methylene chloride and 10 ml of methanol. The insolubles were removed by filtration. The filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (eluant: chloroform/methanol=10/1 to 5/1) to obtain 4.29 g (yield: 77.9%) of (3R,5R,6R)-6-amino-3-(p-nitrobenzyloxycarbonyl)-7-oxo-3-(2-oxo-3-ureidoimidazolidin-1-yl)-4-thia-1-azabicyclo[3.2.0]heptane.

後処理

  1. filtrationThe reaction mixture was filtered
  2. additionTo the filtrate were added 50 ml of ethyl acetate and 50 ml of water
  3. customThe aqueous layer was separated
  4. extractionThe organic layer was extracted three times each with 30 ml of water
  5. customobtained previously
  6. customThe solvent was removed by distillation under reduced pressure
  7. additionTo the resulting residue was added a mixed solvent
  8. customThe insolubles were removed by filtration
  9. concentrationThe filtrate was concentrated under reduced pressure
  10. customThe residue was purified by column chromatography (eluant: chloroform/methanol=10/1 to 5/1)

出典と根拠

ORDレコード
ord-077edc4166ba41658b65011f15938326
出典データセット
uspto-grants-1993_02
特許番号
US05185330

反応ノート

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