Sodium Iodide → Benzhydryl 7beta-[2-difluoromethoxyimino-2-(2-tritylaminothiazol-4-yl)acetamido]-3-(2-methyl-1-pyrazolio)methyl-3-cephem-4-carboxylate chloride

HRID 1088057Notes

Reaction equation

HRID 1088057 reaction equation
[F:1][CH:2]([F:61])[O:3][N:4]=[C:5]([C:36]1[N:37]=[C:38]([NH:41][C:42]([C:55]2[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=2)([C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=2)[C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[S:39][CH:40]=1)[C:6]([NH:8][C@@H:9]1[C:34](=[O:35])[N:11]2[C:12]([C:18]([O:20][CH:21]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[O:19])=[C:13]([CH2:16][Cl:17])[CH2:14][S:15][C@H:10]12)=[O:7].[CH3:62][N:63]1[CH:67]=[CH:66][CH:65]=[N:64]1.[I-].[Na+]>CC(C)=O>[Cl-:17].[F:1][CH:2]([F:61])[O:3][N:4]=[C:5]([C:36]1[N:37]=[C:38]([NH:41][C:42]([C:55]2[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=2)([C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=2)[C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[S:39][CH:40]=1)[C:6]([NH:8][C@@H:9]1[C:34](=[O:35])[N:11]2[C:12]([C:18]([O:20][CH:21]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[O:19])=[C:13]([CH2:16][N+:64]3[N:63]([CH3:62])[CH:67]=[CH:66][CH:65]=3)[CH2:14][S:15][C@H:10]12)=[O:7]

Participants

5

Reactant 3

HCID 5238Sodium IodideHCID 702551H-Pyrazole, 1-methyl-HCID 131716601Benzhydryl 7beta-[2-(2-tritylaminothiazol-4-yl)-2-difluoromethoxyiminoacetamido]-3-chloromethyl-3-cephem-4-carboxylate

Product 1

HCID 178480375Benzhydryl 7beta-[2-difluoromethoxyimino-2-(2-tritylaminothiazol-4-yl)acetamido]-3-(2-methyl-1-pyrazolio)methyl-3-cephem-4-carboxylate chlorideYield 83.5%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

A mixture of benzhydryl 7β-[2-difluoromethoxyimino-2-(2-tritylaminothiazol-4-yl)acetamido]-3-chloromethyl-3-cephem-4-carboxylate (syn isomer, 8.76 g), N-methylpyrazole (8.76 g), sodium iodide (1.5 g) and acetone (9 ml) was stirred at ambient temperature for 19 hours The reaction mixture was evaporated, and ethyl acetate (200 ml) and 5% aqueous solution of sodium thiosulfate were added to the residue. The organic layer was separated and tetrahydrofuran (100 ml) was added thereto. The solution was dried over magnesium sulfate and evaporated and the residue was dissolved in a mixture of tetrahydrofuran (200 ml) and water (65 ml). The solution was subjected to column chromatography on an ion-exchange resin "Amberlite IRA-400" (Cl⃝ form), and eluted with a mixture of tetrahydrofuran and water (15:1 V/V). The fractions containing the object compound were collected, combined and evaporated. The residue was triturated with diisopropyl ether to give benzhydryl 7β-[2-difluoromethoxyimino-2-(2-tritylaminothiazol-4-yl)acetamido]-3-(2-methyl-1-pyrazolio)methyl-3-cephem-4-carboxylate chloride (syn isomer, 8.0 g).

Workup

  1. customwas evaporated
  2. additionethyl acetate (200 ml) and 5% aqueous solution of sodium thiosulfate were added to the residue
  3. customThe organic layer was separated
  4. additiontetrahydrofuran (100 ml) was added
  5. dry with materialThe solution was dried over magnesium sulfate
  6. customevaporated
  7. dissolutionthe residue was dissolved in a mixture of tetrahydrofuran (200 ml) and water (65 ml)
  8. wash" (Cl⃝ form), and eluted with a mixture of tetrahydrofuran and water (15:1 V/V)
  9. additionThe fractions containing the object compound
  10. customwere collected
  11. customevaporated
  12. customThe residue was triturated with diisopropyl ether

Sources & evidence

ORD record
ord-137d5ce6cfaa46f6b8aff561b74a4173
Source dataset
uspto-grants-1990_10
Patent number
US04960766

Reaction notes

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