Phosphate → benzhydryl (6R,7R)-7-[[(2Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-[2-methyl-1-[(2-methylpropan-2-yl)oxy]-1-oxopropan-2-yl]oxyiminoacetyl]amino]-3-(iodomethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

HRID 1247774Notes

Reaction equation

HRID 1247774 reaction equation
[NH2:1][C:2]1[S:6][N:5]=[C:4](/[C:7](=[N:38]/[O:39][C:40]([C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])([CH3:42])[CH3:41])/[C:8]([NH:10][C@@H:11]2[C:36](=[O:37])[N:13]3[C:14]([C:20]([O:22][CH:23]([C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)[C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)=[O:21])=[C:15]([CH2:18]Cl)[CH2:16][S:17][C@H:12]23)=[O:9])[N:3]=1.[I-:50].[Na+].P([O-])([O-])([O-])=O.C(OCC)(=O)C>C1(C)C=CC=CC=1.[Cl-].C(C([NH3+])(C(=O)CCCCCCC)C(=O)CCCCCCC)(=O)CCCCCCC.O>[NH2:1][C:2]1[S:6][N:5]=[C:4](/[C:7](=[N:38]/[O:39][C:40]([C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])([CH3:42])[CH3:41])/[C:8]([NH:10][C@@H:11]2[C:36](=[O:37])[N:13]3[C:14]([C:20]([O:22][CH:23]([C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)[C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)=[O:21])=[C:15]([CH2:18][I:50])[CH2:16][S:17][C@H:12]23)=[O:9])[N:3]=1

Participants

8

Reactant 4

HCID 1061PhosphateHCID 5238Sodium IodideHCID 8857Ethyl AcetateHCID 87787298benzhydryl (6R,7R)-7-[[(2Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-[2-methyl-1-[(2-methylpropan-2-yl)oxy]-1-oxopropan-2-yl]oxyiminoacetyl]amino]-3-(chloromethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

Product 1

HCID 87844717benzhydryl (6R,7R)-7-[[(2Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-[2-methyl-1-[(2-methylpropan-2-yl)oxy]-1-oxopropan-2-yl]oxyiminoacetyl]amino]-3-(iodomethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylateYield 87.9%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 77620884Tricaprylylmethyl ammonium chlorideSolvent

Procedure

To a solution of benzhydryl 7β-[(Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(1-tert-butoxycarbonyl-1-methylethoxyimino)acetamido]-3-chloromethyl-3-cephem-4-carboxylate (60 g) in toluene (600 ml) were added a solution of sodiumiodide (61.8 g) in 0.05 mol phosphate buffer (pH 7, 500 ml) and tricaprylylmethylammonium chloride (6.67 g). The mixture was stirred at room temperature for 15 hours. The reaction mixture was added to a mixture of ethyl acetate and water. The organic layer was washed with water and brine, and then dried over magnesium sulfate. The magnesium sulfate was filtered off, and the filtrate was evaporated to 255 g under reduced pressure. The concentrate was poured into diisopropyl ether (2 L). The resulting precipitate was collected by filtration and dried to give benzhydryl 7β-[(Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(1-tert-butoxycarbonyl-1-methylethoxyimino)acetamido]-3-iodomethyl-3-cephem-4-carboxylate (59.4 g).

Workup

  1. washThe organic layer was washed with water and brine
  2. dry with materialdried over magnesium sulfate
  3. filtrationThe magnesium sulfate was filtered off
  4. customthe filtrate was evaporated to 255 g under reduced pressure
  5. additionThe concentrate was poured into diisopropyl ether (2 L)
  6. filtrationThe resulting precipitate was collected by filtration
  7. customdried

Sources & evidence

ORD record
ord-d24e9c35c4594a029def2e0e2f2ebd9e
Source dataset
uspto-grants-2006_10
Patent number
US07129232B2

Reaction notes

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