Ethyl Acetate → 7beta-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(1-carboxy-1-methylethoxyimino)acetamido]-3-[N,N-dimethyl-N-((5-hydroxy-4-oxo-1,4-dihydropyridin-2-yl)methyl}ammonio]methyl-3-cephem-4-carboxylate

HRID 1734263Notes

Reaction equation

HRID 1734263 reaction equation
Cl.Cl.[NH2:3][C@@H:4]1[C:27](=[O:28])[N:6]2[C:7]([C:24]([O-:26])=[O:25])=[C:8]([CH2:11][N+:12]([CH3:23])([CH3:22])[CH2:13][C:14]3[NH:15][CH:16]=[C:17]([OH:21])[C:18](=[O:20])[CH:19]=3)[CH2:9][S:10][C@H:5]12.C[Si](C)(C)NC(=O)C.CS([O:41][C:42](=O)[C:43]([C:52]1[N:56]=[C:55]([NH2:57])[S:54][N:53]=1)=[N:44][O:45][C:46]([C:49]([OH:51])=[O:50])([CH3:48])[CH3:47])(=O)=O.C(OCC)(=O)C>O1CCCC1>[NH2:57][C:55]1[S:54][N:53]=[C:52]([C:43](=[N:44][O:45][C:46]([C:49]([OH:51])=[O:50])([CH3:48])[CH3:47])[C:42]([NH:3][C@@H:4]2[C:27](=[O:28])[N:6]3[C:7]([C:24]([O-:26])=[O:25])=[C:8]([CH2:11][N+:12]([CH3:23])([CH3:22])[CH2:13][C:14]4[NH:15][CH:16]=[C:17]([OH:21])[C:18](=[O:20])[CH:19]=4)[CH2:9][S:10][C@H:5]23)=[O:41])[N:56]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 25989Acetamide, N-(trimethylsilyl)-HCID 537830312-(5-Amino-1,2,4-thiadiazol-3-yl)-2-(1-carboxy-1-methylethoxyimino)acetic methanesulfonic anhydrideHCID 677480537beta-amino-3-[N,N-dimethyl-N-{(5-hydroxy-4-oxo-1,4-dihydropyridin-2-yl)methyl}ammonio]methyl-3-cephem-4carboxylate dihydrochloride

Product 1

HCID 1317181237beta-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(1-carboxy-1-methylethoxyimino)acetamido]-3-[N,N-dimethyl-N-((5-hydroxy-4-oxo-1,4-dihydropyridin-2-yl)methyl}ammonio]methyl-3-cephem-4-carboxylateYield 47.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
35 °C

Procedure

7β-Amino-3-[N,N-dimethyl-N-{(5-hydroxy-4-oxo-1,4-dihydropyridin-2-yl)methyl}ammonio]methyl-3-cephem-4-carboxylate dihydrochloride (181 mg) was suspended in tetrahydrofuran (9.1 ml). To the suspension was added N-(trimethylsilyl)acetamide (788 mg), and the mixture was stirred at 35° C. for 30 minutes and cooled to 5° C. To the resulting solution was added a solution of 2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(1-carboxy-1-methylethoxyimino)acetic methanesulfonic anhydride (syn isomer) (169 mg) in tetrahydrofuran (0.5 ml). The mixture was warmed to 20° C. and stirred for 1.2 hours. The mixture was poured into ethyl acetate (200 ml) and the resulting precipitates were collected by filtration, washed with ethyl acetate and diisopropyl ether and dried in vacuo. The powder was suspended in water (40 ml) and adjusted to pH 1 with 1N hydrochloric acid. After the insoluble materials were removed by filtration, the filtrate was chromatographed on Diaion HP-20 (15 ml) and the elution was carried out with 15% aqueous isopropyl alcohol. The eluate was lyophilized to give 7β-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(1-carboxy-1-methylethoxyimino)acetamido]-3-[N,N-dimethyl-N-{(5-hydroxy-4-oxo-1,4-dihydropyridin-2-yl)methyl}ammonio]methyl-3-cephem-4-carboxylate (syn isomer) (120 mg).

Workup

  1. temperaturecooled to 5° C
  2. temperatureThe mixture was warmed to 20° C.
  3. stirringstirred for 1.2 hours
  4. customthe resulting precipitates
  5. filtrationwere collected by filtration
  6. washwashed with ethyl acetate and diisopropyl ether
  7. customdried in vacuo
  8. customAfter the insoluble materials were removed by filtration
  9. customthe filtrate was chromatographed on Diaion HP-20 (15 ml)
  10. washthe elution

Sources & evidence

ORD record
ord-16b0161642894ea8873e8fcd84200f35
Source dataset
uspto-grants-1996_07
Patent number
US05532354

Reaction notes

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