碘化钠 → 4-O-tert-butyl 1-O-[(4-methoxyphenyl)methyl] (2S)-2-[(Z)-[2-[[(5R,6R,7R)-2-benzhydryloxycarbonyl-3-(iodomethyl)-5,8-dioxo-5lambda4-thia-1-azabicyclo[4.2.0]oct-2-en-7-yl]amino]-1-[5-chloro-2-[(2-methylpropan-2-yl)oxycarbonylamino]-1,3-thiazol-4-yl]-2-oxoethylidene]amino]oxybutanedioate

HRID 525914笔记

反应方程式

HRID 525914 反应方程式
[CH:1]([O:14][C:15]([C:17]1[N:18]2[C@H:21]([S@:22](=[O:27])[CH2:23][C:24]=1[CH2:25]Cl)[C@H:20]([NH:28][C:29](=[O:68])/[C:30](=[N:45]\[O:46][C@@H:47]([CH2:60][C:61]([O:63][C:64]([CH3:67])([CH3:66])[CH3:65])=[O:62])[C:48]([O:50][CH2:51][C:52]1[CH:57]=[CH:56][C:55]([O:58][CH3:59])=[CH:54][CH:53]=1)=[O:49])/[C:31]1[N:32]=[C:33]([NH:37][C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[S:34][C:35]=1[Cl:36])[C:19]2=[O:69])=[O:16])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[I-:70].[Na+]>C(#N)C>[CH:1]([O:14][C:15]([C:17]1[N:18]2[C@H:21]([S@:22](=[O:27])[CH2:23][C:24]=1[CH2:25][I:70])[C@H:20]([NH:28][C:29](=[O:68])/[C:30](=[N:45]\[O:46][C@@H:47]([CH2:60][C:61]([O:63][C:64]([CH3:67])([CH3:66])[CH3:65])=[O:62])[C:48]([O:50][CH2:51][C:52]1[CH:57]=[CH:56][C:55]([O:58][CH3:59])=[CH:54][CH:53]=1)=[O:49])/[C:31]1[N:32]=[C:33]([NH:37][C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[S:34][C:35]=1[Cl:36])[C:19]2=[O:69])=[O:16])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

参与物

4

反应物 2

HCID 5238碘化钠HCID 903733644-O-tert-butyl 1-O-[(4-methoxyphenyl)methyl] (2S)-2-[(Z)-[2-[[(5R,6R,7R)-2-benzhydryloxycarbonyl-3-(chloromethyl)-5,8-dioxo-5lambda4-thia-1-azabicyclo[4.2.0]oct-2-en-7-yl]amino]-1-[5-chloro-2-[(2-methylpropan-2-yl)oxycarbonylamino]-1,3-thiazol-4-yl]-2-oxoethylidene]amino]oxybutanedioate

产物 1

HCID 903733704-O-tert-butyl 1-O-[(4-methoxyphenyl)methyl] (2S)-2-[(Z)-[2-[[(5R,6R,7R)-2-benzhydryloxycarbonyl-3-(iodomethyl)-5,8-dioxo-5lambda4-thia-1-azabicyclo[4.2.0]oct-2-en-7-yl]amino]-1-[5-chloro-2-[(2-methylpropan-2-yl)oxycarbonylamino]-1,3-thiazol-4-yl]-2-oxoethylidene]amino]oxybutanedioate收率 59.9%

试剂、催化剂与溶剂 1

HCID 6342乙腈溶剂

实验过程

To a solution of (S)-4-tert-butyl 1-(4-methoxybenzyl) 2-(((Z)-(2-(((5R,6R,7R)-2-((benzhydryloxy)carbonyl)-3-(chloromethyl)-5-oxido-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-7-yl)amino)-1-(2-((tert-butoxycarbonyl)amino)-5-chlorothiazol-4-yl)-2-oxoethylidene)amino)oxy)succinate (27 g, 24.98 mmol) in Acetonitrile (300 mL) was added sodium iodide (5.62 g, 37.5 mmol). The mixture was stirred at room temperature over 1.5 h. LCMS indicated completion of the reaction. The solid was filtered off, the filtrate was concentrated under vacuum, and the residue was purified by CombiFlash Rf automated silica gel chromatography (330 g column), eluting with EtOAc/Hexanes (0-50%) to afford (S)-4-tert-butyl 1-(4-methoxybenzyl) 2-(((Z)-(2-(((5R,6R,7R)-2-((benzhydryloxy)carbonyl)-3-(iodomethyl)-5-oxido-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-7-yl)amino)-1-(2-((tert-butoxycarbonyl)amino)-5-chlorothiazol-4-yl)-2-oxoethylidene)amino)oxy)succinate (18 g, 14.97 mmol, 59.9% yield) as a red-brown solid. LCMS: (M+H)+: 1118.1

后处理

  1. customcompletion of the reaction
  2. filtrationThe solid was filtered off
  3. concentrationthe filtrate was concentrated under vacuum
  4. customthe residue was purified by CombiFlash Rf automated silica gel chromatography (330 g column)
  5. washeluting with EtOAc/Hexanes (0-50%)

来源与证据

ORD记录
ord-ea04e896d0fb4e32bb7555ef89dc4d36
来源数据集
uspto-grants-2016_05
专利号
US09340556B2

反应笔记

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