Ethyl Acetate → Benzhydryl 7beta-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-carboxymethoxyiminoacetamido]-3-chloromethyl-3-cephem-4-carboxylate

HRID 1609666Notes

Reaction equation

HRID 1609666 reaction equation
Cl.[NH2:2][C@@H:3]1[C:28](=[O:29])[N:5]2[C:6]([C:12]([O:14][CH:15]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[O:13])=[C:7]([CH2:10][Cl:11])[CH2:8][S:9][C@H:4]12.C[Si](C)(C)NC(=O)C.CS([O:42][C:43](=O)[C:44]([C:51]1[N:55]=[C:54]([NH2:56])[S:53][N:52]=1)=[N:45][O:46][CH2:47][C:48]([OH:50])=[O:49])(=O)=O.C(OCC)(=O)C>O1CCCC1.O>[NH2:56][C:54]1[S:53][N:52]=[C:51]([C:44](=[N:45][O:46][CH2:47][C:48]([OH:50])=[O:49])[C:43]([NH:2][C@@H:3]2[C:28](=[O:29])[N:5]3[C:6]([C:12]([O:14][CH:15]([C:16]4[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=4)[C:22]4[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=4)=[O:13])=[C:7]([CH2:10][Cl:11])[CH2:8][S:9][C@H:4]23)=[O:42])[N:55]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 25989Acetamide, N-(trimethylsilyl)-HCID 132396287-Amino-3-chloromethyl-3-cephem-4-carboxylic acid diphenylmethyl ester hydrochlorideHCID 536554152-(5-Amino-1,2,4-thiadiazol-3-yl)-2-carboxymethoxyiminoacetic methanesulfonic anhydride

Product 1

HCID 131718944Benzhydryl 7beta-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-carboxymethoxyiminoacetamido]-3-chloromethyl-3-cephem-4-carboxylateYield 53.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of benzhydryl 7β-amino-3-chloromethyl-3-cephem-4-carboxylate hydrochloride (22.6 g) and N-trimethylsilylacetamide (25.0 g) in tetrahydrofuran (250 ml) was added 2-(5-amino-1,2,4-thiadiazol-3-yl) -2-carboxymethoxyiminoacetic methanesulfonic anhydride (syn isomer) (19.8 g) at 0°-5° C. under Stirring. The stirring was continued for an hour at the same temperature. The reaction mixture was poured into a mixture of ethyl acetate (500 ml) and water (500 ml). The organic layer was separated, washed with water twice and a saturated aqueous solution of sodium chloride, dried over magnesium sulfate and then concentrated in vacuo. To the residue was added diethyl ether and then the resulting precipitates were collected by filtration to give benzhydryl 7β-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-carboxymethoxyiminoacetamido]-3-chloromethyl-3-cephem-4-carboxylate (syn isomer) (17.2 g).

Workup

  1. waitThe stirring was continued for an hour at the same temperature
  2. customThe organic layer was separated
  3. washwashed with water twice
  4. dry with materiala saturated aqueous solution of sodium chloride, dried over magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. additionTo the residue was added diethyl ether
  7. customthe resulting precipitates
  8. filtrationwere collected by filtration

Sources & evidence

ORD record
ord-0a8b761adee24f60abf51a45a1617f2f
Source dataset
uspto-grants-1995_03
Patent number
US05401734

Reaction notes

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