Chloroform → benzhydryl 7-[2-allyloxyimino-2-(5-amino-1,2,4-thiadiazol-3-yl)acetamido]-3-[(Z)-2-(2-pyridyl)vinylthio]-3-cephem-4-carboxylate

HRID 704267Notes

Reaction equation

HRID 704267 reaction equation
[NH2:1][CH:2]1[C:34](=[O:35])[N:4]2[C:5]([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:6]([S:9]/[CH:10]=[CH:11]\[C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=3)[CH2:7][S:8][C@H:3]12.C[Si](NC(=O)N[Si](C)(C)C)(C)C.Cl.[CH2:49]([O:52][N:53]=[C:54]([C:58]1[N:62]=[C:61]([NH2:63])[S:60][N:59]=1)[C:55](Cl)=[O:56])[CH:50]=[CH2:51].C(Cl)(Cl)Cl>C(Cl)Cl.O1CCCC1.C(OCC)(=O)C.C(=O)(O)[O-].[Na+].O>[CH2:49]([O:52][N:53]=[C:54]([C:58]1[N:62]=[C:61]([NH2:63])[S:60][N:59]=1)[C:55]([NH:1][CH:2]1[C:34](=[O:35])[N:4]2[C:5]([C:18]([O:20][CH:21]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=3)=[O:19])=[C:6]([S:9]/[CH:10]=[CH:11]\[C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=3)[CH2:7][S:8][C@H:3]12)=[O:56])[CH:50]=[CH2:51]

Participants

10

Reactant 4

HCID 6212ChloroformHCID 875621,3-Bis(trimethylsilyl)ureaHCID 67948085benzhydryl 7-amino-3-[(Z)-2-(2-pyridyl)vinylthio]-3-cephem-4-carboxylateHCID 736584962-Allyloxyimino-2-(5-amino-1,2,4-thiadiazol-3-yl)acetyl chloride hydrochloride

Product 1

HCID 131716151benzhydryl 7-[2-allyloxyimino-2-(5-amino-1,2,4-thiadiazol-3-yl)acetamido]-3-[(Z)-2-(2-pyridyl)vinylthio]-3-cephem-4-carboxylate

Reagents, catalysts & solvents 5

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Procedure

A mixture of benzhydryl 7-amino-3-[(Z)-2-(2-pyridyl)vinylthio]-3-cephem-4-carboxylate (600 ml) and bis(trimethylsilyl)urea (981 mg) in methylene chloride (6 ml) was stirred at 30°~35° C. for 30 minutes to give a clear solution. To the clear solution was added 2-allyloxyimino-2-(5-amino-1,2,4-thiadiazol-3-yl)acetyl chloride monohydrochloride (syn isomer) (480 mg) at 20° C. and the mixture was stirred for 30 minutes at -10°~-15° C. The mixture was poured into a mixture of chloroform and water. The organic layer was separated and concentrated in vacuo to give a residue. The residue was dissolved in a mixture of tetrahydrofuran, ethyl acetate and dilute aqueous solution of sodium bicarbonate. The organic layer was separated, washed with dilute aqueous solution of sodium bicarbonate and a saturated aqueous solution of sodium chloride in turn, dried over magnesium sulfate and concentrated in vacuo, and the residue was triturated with diisopropyl ether to give benzhydryl 7-[2-allyloxyimino-2-(5-amino-1,2,4-thiadiazol-3-yl)acetamido]-3-[(Z)-2-(2-pyridyl)vinylthio]-3-cephem-4-carboxylate (syn isomer) (848 mg).

Workup

  1. customto give a clear solution
  2. stirringthe mixture was stirred for 30 minutes at -10°~-15° C
  3. customThe organic layer was separated
  4. concentrationconcentrated in vacuo
  5. customto give a residue
  6. customThe organic layer was separated
  7. washwashed with dilute aqueous solution of sodium bicarbonate
  8. dry with materiala saturated aqueous solution of sodium chloride in turn, dried over magnesium sulfate
  9. concentrationconcentrated in vacuo
  10. customthe residue was triturated with diisopropyl ether

Sources & evidence

ORD record
ord-5fe170c5074a4935ba37d8ce4b969c32
Source dataset
uspto-grants-1991_01
Patent number
US04985555

Reaction notes

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