Sodium Iodide → 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 525914Notes

Reaction equation

HRID 525914 reaction equation
[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

Participants

4

Reactant 2

HCID 5238Sodium IodideHCID 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

Product 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]oxybutanedioateYield 59.9%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

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

Workup

  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%)

Sources & evidence

ORD record
ord-ea04e896d0fb4e32bb7555ef89dc4d36
Source dataset
uspto-grants-2016_05
Patent number
US09340556B2

Reaction notes

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