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对甲苯磺酰氯 → 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
笔记
打印预览

反应方程式

HRID 463583 反应方程式
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
参与物反应条件实验过程后处理来源与证据反应笔记

参与物

9

反应物 4

HCID 7397对甲苯磺酰氯HCID 130352,2,6,6-四甲基哌啶HCID 132333103-Acetonyl-2-benzhydryloxycarbonyl-7-t-butoxycarbonylamino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-eneHCID 178418339正丁基锂

产物 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收率 28.6%

试剂、催化剂与溶剂 4

HCID 8028四氢呋喃溶剂3 次HCID 8058正己烷溶剂HCID 8857乙酸乙酯溶剂HCID 12679六甲基磷酰三胺溶剂

反应条件

温度
20 °C

实验过程

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.

后处理

  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

来源与证据

ORD记录
ord-4e8eb080714242ae87a995c08534ec0f
来源数据集
uspto-grants-1985_05
DOI
10.6084/m9.figshare.5104873.v1
专利号
US04520193

反应笔记

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本页导航参与物反应条件实验过程后处理来源与证据反应笔记