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4-Toluenesulfonyl chloride → 2-Benzhydryloxycarbonyl-7-t-butoxycarbonylamino-3-(2-tosyloxyprop-1-en-1-yl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene

HRID 463583
ノート
印刷プレビュー

反応式

HRID 463583 の反応式
C([Li])CCC.CC1(C)CCCC(C)(C)N1.[CH2:16]([C:20]1[CH2:27][S:26][CH:25]2[N:22]([C:23](=[O:36])[CH:24]2[NH:28][C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[C:21]=1[C:37]([O:39][CH:40]([C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1)[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)=[O:38])[C:17]([CH3:19])=[O:18].[C:53]1([CH3:63])[CH:58]=[CH:57][C:56]([S:59](Cl)(=[O:61])=[O:60])=[CH:55][CH:54]=1>CCCCCC.O1CCCC1.C(OCC)(=O)C.CN(P(N(C)C)(N(C)C)=O)C>[CH:40]([O:39][C:37]([C:21]1[N:22]2[CH:25]([S:26][CH2:27][C:20]=1[CH:16]=[C:17]([O:18][S:59]([C:56]1[CH:57]=[CH:58][C:53]([CH3:63])=[CH:54][CH:55]=1)(=[O:61])=[O:60])[CH3:19])[CH:24]([NH:28][C:29]([O:31][C:32]([CH3:35])([CH3:33])[CH3:34])=[O:30])[C:23]2=[O:36])=[O:38])([C:47]1[CH:48]=[CH:49][CH:50]=[CH:51][CH:52]=1)[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

9

反応物 4

HCID 73974-Toluenesulfonyl chlorideHCID 130352,2,6,6-TetramethylpiperidineHCID 132333103-Acetonyl-2-benzhydryloxycarbonyl-7-t-butoxycarbonylamino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-eneHCID 178418339Butyllithium

生成物 1

HCID 539916602-Benzhydryloxycarbonyl-7-t-butoxycarbonylamino-3-(2-tosyloxyprop-1-en-1-yl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene
収率 28.6%

試薬・触媒・溶媒 4

HCID 8028Tetrahydrofuran溶媒3 回HCID 8058Hexane溶媒HCID 8857Ethyl Acetate溶媒HCID 12679Hexamethylphosphoramide溶媒

反応条件

温度
20 °C

実験手順

A 1.6M solution of butyllithium in hexane (3.44 cc) is added, in the course of 10 minutes, to a solution of 2,2,6,6-tetramethylpiperidine (0.78 g) in tetrahydrofuran (5 cc) at 20° C. The solution is stirred for 10 minutes at 20° C. and then cooled to -70° C. A solution of 3-acetonyl-2-benzhydryloxycarbonyl-7-t-butoxycarbonylamino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene (2.54 g) in tetrahydrofuran (6 cc) is then added in the course of 20 minutes, and the mixture is then stirred for 15 minutes at -70° C. Hexamethylphosphorotriamide (7 cc) is added in the course of 3 minutes, followed by a solution of p-toluenesulphonyl chloride (5.23 g) in tetrahydrofuran (7 cc) in the course of 3 minutes. The mixture is stirred for 45 minutes at -70° C., the temperature is then left to rise to 0° C. and the solution is diluted with ethyl acetate (100 cc) and washed successively with a 0.1N solution of citric acid (50 cc), a saturated aqueous solution of sodium bicarbonate (50 cc) and distilled water (100 cc). The organic phase is dried over sodium sulphate and concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 20° C. The residue is chromatographed on a column of Merck silica gel (0.06-0.20) (110 g) (diameter of the column: 3 cm; height: 26 cm). Elution is carried out with a 15/80 (by volume) ethyl acetate/cyclohexane mixture (1,200 cc), 60 cc fractions being collected. Fractions 3 to 15 are concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 20° C. This yields the Z form of 2-benzhydryloxycarbonyl-7-t-butoxycarbonylamino-3-(2-tosyloxyprop-1-en-1-yl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene (0.94 g) in the form of a hard, pale yellow foam.

後処理

  1. temperaturecooled to -70° C
  2. stirringthe mixture is then stirred for 15 minutes at -70° C
  3. stirringThe mixture is stirred for 45 minutes at -70° C.
  4. waitthe temperature is then left
  5. customto rise to 0° C.
  6. washwashed successively with a 0.1N solution of citric acid (50 cc)
  7. distillationa saturated aqueous solution of sodium bicarbonate (50 cc) and distilled water (100 cc)
  8. dry with materialThe organic phase is dried over sodium sulphate
  9. concentrationconcentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 20° C
  10. customThe residue is chromatographed on a column of Merck silica gel (0.06-0.20) (110 g) (diameter of the column
  11. washElution
  12. custombeing collected
  13. concentrationFractions 3 to 15 are concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 20° C

出典と根拠

ORDレコード
ord-4e8eb080714242ae87a995c08534ec0f
出典データセット
uspto-grants-1985_05
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US04520193

反応ノート

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このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート