Water → 4-Nitrobenzyl 7-[2-(2-bromoacetyl)acetamido]-3-cephem-4-carboxylate

HRID 435013Notes

Reaction equation

HRID 435013 reaction equation
[NH2:1][CH:2]1[C:22](=[O:23])[N:4]2[C:5]([C:9]([O:11][CH2:12][C:13]3[CH:18]=[CH:17][C:16]([N+:19]([O-:21])=[O:20])=[CH:15][CH:14]=3)=[O:10])=[CH:6][CH2:7][S:8][C@H:3]12.[Br:24]Br.[CH2:26]=[C:27]1[O:31][C:29](=[O:30])[CH2:28]1.O>C[Si](CC(N)=O)(C)C.C[Si](C([Si](C)(C)C)C(N)=O)(C)C.C(OCC)(=O)C.C(Cl)Cl>[Br:24][CH2:31][C:27]([CH2:28][C:29]([NH:1][CH:2]1[C:22](=[O:23])[N:4]2[C:5]([C:9]([O:11][CH2:12][C:13]3[CH:14]=[CH:15][C:16]([N+:19]([O-:21])=[O:20])=[CH:17][CH:18]=3)=[O:10])=[CH:6][CH2:7][S:8][C@H:3]12)=[O:30])=[O:26]

Participants

9

Reactant 4

HCID 962WaterHCID 12661DiketeneHCID 24408BromineHCID 12775080p-Nitrobenzyl 7-amino-3-cephem-4-carboxylate2×

Product 1

HCID 886077454-Nitrobenzyl 7-[2-(2-bromoacetyl)acetamido]-3-cephem-4-carboxylateYield 82.8%

Reagents, catalysts & solvents 4

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolventHCID 357676Acetamide, 2-(trimethylsilyl)-SolventHCID 11708267BistrimethylsilylacetamidSolvent

Conditions

Temperature
45 °C

Procedure

4-Nitrobenzyl 7-amino-3-cephem-4-carboxylate (5 g.) was dissolved in a solution of trimethylsilylacetamide (13.8 g.) and bis(trimethylsilyl)acetamide (10 ml.) in dry ethyl acetate (50 ml.) and stirred at 45° C. for 1.5 hours. A solution of bromine (2.88 g.) in methylene chloride (7 ml.) was added dropwise to a solution of diketene (1.5 g.) in methylene chloride (7 ml.) at -40° C. over 20 minutes and stirred at -30° C. for 1 hour. The solution obtained thus was added to dropwise to the above solution of 4-nitrobenzyl 7-amino-3-cephem-4-carboxylate under cooling at -15° C. and then stirred at the same temperature for 30 minutes. Water (50 ml.) was added to the resultant solution and extracted with ethyl acetate. The ethyl acetate extract was washed with water, dried over magnesium sulfate and concentrated under reduced pressure to give oily 4-nitrobenzyl 7-[2-(2-bromoacetyl)acetamido]-3-cephem-4-carboxylate (6.15 g.)

Workup

  1. stirringstirred at -30° C. for 1 hour
  2. customThe solution obtained thus
  3. temperatureunder cooling at -15° C.
  4. stirringstirred at the same temperature for 30 minutes
  5. extractionextracted with ethyl acetate
  6. extractionThe ethyl acetate extract
  7. washwas washed with water
  8. dry with materialdried over magnesium sulfate
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-ff09ed6f517547e8b5f9bd8150ad85d2
Source dataset
uspto-grants-1983_08
Patent number
US04399133

Reaction notes

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