Sodium Thiosulfate → 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 525919Notes

Reaction equation

HRID 525919 reaction equation
[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]

Participants

5

Reactant 3

HCID 24477Sodium ThiosulfateHCID 70297m-Chloroperbenzoic acidHCID 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

Product 1

HCID 90373324benzhydryl (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-carboxylateYield 91.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

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

Workup

  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)

Sources & evidence

ORD record
ord-a431b3f6fa5d415886d765c7bfd78ada
Source dataset
uspto-grants-2016_05
Patent number
US09340556B2

Reaction notes

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