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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
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HRID 525913 반응식
[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
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

5

반응물 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

생성물 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
수율 94%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

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

후처리

  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%)

출처 및 근거

ORD 기록
ord-fe17b41af4da4abbbd3735ce010d45ff
출처 데이터셋
uspto-grants-2016_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09340556B2

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