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Sodium Thiosulfate → 4-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

HRID 525913
ノート
印刷プレビュー

反応式

HRID 525913 の反応式
[CH:1]([O:14][C:15]([C:17]1[N:18]2[C@H:21]([S:22][CH2:23][C:24]=1[CH2:25][Cl:26])[C@H:20]([NH:27][C:28](=[O:67])/[C:29](=[N:44]\[O:45][C@@H:46]([CH2:59][C:60]([O:62][C:63]([CH3:66])([CH3:65])[CH3:64])=[O:61])[C:47]([O:49][CH2:50][C:51]1[CH:56]=[CH:55][C:54]([O:57][CH3:58])=[CH:53][CH:52]=1)=[O:48])/[C:30]1[N:31]=[C:32]([NH:36][C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[S:33][C:34]=1[Cl:35])[C:19]2=[O:68])=[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.C1C=C(Cl)C=C(C(OO)=[O:77])C=1.[O-]S([O-])(=S)=O.[Na+].[Na+]>ClCCl>[CH:1]([O:14][C:15]([C:17]1[N:18]2[C@H:21]([S@:22](=[O:77])[CH2:23][C:24]=1[CH2:25][Cl:26])[C@H:20]([NH:27][C:28](=[O:67])/[C:29](=[N:44]\[O:45][C@@H:46]([CH2:59][C:60]([O:62][C:63]([CH3:66])([CH3:65])[CH3:64])=[O:61])[C:47]([O:49][CH2:50][C:51]1[CH:52]=[CH:53][C:54]([O:57][CH3:58])=[CH:55][CH:56]=1)=[O:48])/[C:30]1[N:31]=[C:32]([NH:36][C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[S:33][C:34]=1[Cl:35])[C:19]2=[O:68])=[O:16])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
参加物実験手順後処理出典と根拠反応ノート

参加物

5

反応物 3

HCID 24477Sodium ThiosulfateHCID 70297m-Chloroperbenzoic acidHCID 894886674-O-tert-butyl 1-O-[(4-methoxyphenyl)methyl] (2S)-2-[(Z)-[2-[[(6R,7R)-2-benzhydryloxycarbonyl-3-(chloromethyl)-8-oxo-5-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

生成物 1

HCID 90373364
4-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
収率 94%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

To a solution of (S)-4-tert-butyl 1-(4-methoxybenzyl) 2-(((Z)-(2-(((6R,7R)-2-((benzhydryl oxy)carbonyl)-3-(chloromethyl)-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 (27.5 g, 27.2 mmol) in Dichloromethane (DCM) (IL) at −40° C. was added dropwise a solution of m-CPBA (6.40 g, 28.6 mmol) in Dichloromethane (DCM) (200 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 solution was separated and washed with 5% NaHCO3 (400 mL), brine (400 mL), dried (Na2SO4), filtered, and concentrated (temperature of the water bath should not be too high—apx. 25° C.). The residue was purified by CombiFlash automated silica gel chromatography (220 g column), eluting with EtOAc/Hexanes (0-60%) to afford (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 (27.5 g, 25.4 mmol, 94% yield) as a light yellow foaming solid. LCMS: (M+H)+: 1026.3

後処理

  1. customcompletion of the reaction
  2. customThe organic solution was separated
  3. washwashed with 5% NaHCO3 (400 mL), brine (400 mL)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated (temperature of the water bath should not
  7. custom25° C.
  8. customThe residue was purified by CombiFlash automated silica gel chromatography (220 g column)
  9. washeluting with EtOAc/Hexanes (0-60%)

出典と根拠

ORDレコード
ord-fe17b41af4da4abbbd3735ce010d45ff
出典データセット
uspto-grants-2016_05
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09340556B2

反応ノート

読み込み中…

このページの内容参加物実験手順後処理出典と根拠反応ノート