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硫代硫酸钠 → benzhydryl (5R,6R,7R)-3-(chloromethyl)-7-[[(2Z)-2-[5-chloro-2-[(2-methylpropan-2-yl)oxycarbonylamino]-1,3-thiazol-4-yl]-2-[2-methyl-1-[(2-methylpropan-2-yl)oxy]-1-oxopropan-2-yl]oxyiminoacetyl]amino]-5,8-dioxo-5lambda4-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

HRID 525919
笔记
打印预览

反应方程式

HRID 525919 反应方程式
[C:1]([O:5][C:6](=[O:57])[C:7]([O:10]/[N:11]=[C:12](/[C:43]1[N:44]=[C:45]([NH:49][C:50]([O:52][C:53]([CH3:56])([CH3:55])[CH3:54])=[O:51])[S:46][C:47]=1[Cl:48])\[C:13]([NH:15][C@@H:16]1[C:23](=[O:24])[N:22]2[C@@H:17]1[S:18][CH2:19][C:20]([CH2:41][Cl:42])=[C:21]2[C:25]([O:27][CH:28]([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:26])=[O:14])([CH3:9])[CH3:8])([CH3:4])([CH3:3])[CH3:2].C1C=C(Cl)C=C(C(OO)=[O:66])C=1.[O-]S([O-])(=S)=O.[Na+].[Na+]>ClCCl>[C:1]([O:5][C:6](=[O:57])[C:7]([O:10]/[N:11]=[C:12](/[C:43]1[N:44]=[C:45]([NH:49][C:50]([O:52][C:53]([CH3:56])([CH3:55])[CH3:54])=[O:51])[S:46][C:47]=1[Cl:48])\[C:13]([NH:15][C@@H:16]1[C:23](=[O:24])[N:22]2[C@@H:17]1[S@:18](=[O:66])[CH2:19][C:20]([CH2:41][Cl:42])=[C:21]2[C:25]([O:27][CH:28]([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:26])=[O:14])([CH3:8])[CH3:9])([CH3:2])([CH3:3])[CH3:4]
参与物实验过程后处理来源与证据反应笔记

参与物

5

反应物 3

HCID 24477硫代硫酸钠HCID 70297间氯过氧苯甲酸HCID 90373529benzhydryl (6R,7R)-3-(chloromethyl)-7-[[(2Z)-2-[5-chloro-2-[(2-methylpropan-2-yl)oxycarbonylamino]-1,3-thiazol-4-yl]-2-[2-methyl-1-[(2-methylpropan-2-yl)oxy]-1-oxopropan-2-yl]oxyiminoacetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

产物 1

HCID 90373324
benzhydryl (5R,6R,7R)-3-(chloromethyl)-7-[[(2Z)-2-[5-chloro-2-[(2-methylpropan-2-yl)oxycarbonylamino]-1,3-thiazol-4-yl]-2-[2-methyl-1-[(2-methylpropan-2-yl)oxy]-1-oxopropan-2-yl]oxyiminoacetyl]amino]-5,8-dioxo-5lambda4-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate
收率 91.6%

试剂、催化剂与溶剂 1

HCID 6344二氯甲烷溶剂2 次

实验过程

To a solution of (6R,7R)-benzhydryl 7-((Z)-2-(((1-(tert-butoxy)-2-methyl-1-oxopropan-2-yl)oxy)imino)-2-(2-((tert-butoxycarbonyl)amino)-5-chlorothiazol-4-yl)acetamido)-3-(chloromethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate (29.9 g, 34.7 mmol) in Dichloromethane (DCM) (1.1 L) at −40° C. was added dropwise a solution of m-CPBA (8.17 g, 36.5 mmol) in Dichloromethane (DCM) (220 mL) over 10 min. The mixture was stirred at the same temperature over 30 min. LCMS indicated completion of the reaction. The mixture was treated with 15% aq. Na2S2O3 (200 mL). The organic phase was separated and washed with 5% NaHCO3 (400 mL), brine (400 mL), dried (Na2SO4), filtered, and concentrated. The residue was purified by CombiFlash automated silica gel chromatography (330 g column, 0-50% EtOAc/Hexanes) to afford (5R,6R,7R)-benzhydryl 7-((Z)-2-(((1-(tert-butoxy)-2-methyl-1-oxopropan-2-yl)oxy)imino)-2-(2-((tert-butoxycarbonyl)amino)-5-chlorothiazol-4-yl)acetamido)-3-(chloromethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate 5-oxide (29 g, 31.8 mmol, 91% yield) as a light yellow solid. LCMS: (M+H)+: 876.3

后处理

  1. customcompletion of the reaction
  2. customThe organic phase was separated
  3. washwashed with 5% NaHCO3 (400 mL), brine (400 mL)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by CombiFlash automated silica gel chromatography (330 g column, 0-50% EtOAc/Hexanes)

来源与证据

ORD记录
ord-a431b3f6fa5d415886d765c7bfd78ada
来源数据集
uspto-grants-2016_05
DOI
10.6084/m9.figshare.5104873.v1
专利号
US09340556B2

反应笔记

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本页导航参与物实验过程后处理来源与证据反应笔记