Water → 7-[2-(2-Bromoacetyl)acetamido]-3-cephem-4-carboxylic acid

HRID 2296217Notes

Reaction equation

HRID 2296217 reaction equation
[NH2:1][CH:2]1[C:12](=[O:13])[N:4]2[C:5]([C:9]([OH:11])=[O:10])=[CH:6][CH2:7][S:8][C@H:3]12.[Br:14]Br.[CH2:16]=[C:17]1[O:21][C:19](=[O:20])[CH2:18]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:14][CH2:21][C:17]([CH2:18][C:19]([NH:1][CH:2]1[C:12](=[O:13])[N:4]2[C:5]([C:9]([OH:11])=[O:10])=[CH:6][CH2:7][S:8][C@H:3]12)=[O:20])=[O:16]

Participants

9

Reactant 4

HCID 962WaterHCID 12661DiketeneHCID 24408BromineHCID 12941984(6R)-7-amino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid2×

Product 1

HCID 886081427-[2-(2-Bromoacetyl)acetamido]-3-cephem-4-carboxylic acidYield 61.2%

Reagents, catalysts & solvents 4

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

Procedure

7-Amino-3-cephem-4-carboxylic acid (2.54 g.) was dissolved in a solution of trimethylsilylacetamide (11.7 g.) and bis(trimethylsilyl)acetamide (15 ml.) in dried ethyl acetate (50 ml.) A solution of bromine (2.43 g.) in dried methylene chloride (10 ml.) was added dropwise to a solution of diketene (1.28 g.) in dried methylene chloride (25 ml.) at -30° C. over 10 minutes and stirred at the same temperature for 1.5 hours. The solution was added to the above solution containing 7-amino-3-cephem-4-carboxylic acid at -15° C. over 10 minutes, and stirred at -15° to -10° C. for 1.5 hours. Water (50 ml.) was added to the resultant solution. The ethyl acetate layer was separated, and extracted with aqueous solution of sodium bicarbonate. The aqueous extract was adjusted to pH 2.0 with 10% hydrochloric acid and extracted with ethyl acetate. The ethyl acetate extract was washed with water, dried over magnesium sulfate and concentrated under reduced pressure to give 7-[2-(2-bromoacetyl)acetamido]-3-cephem-4-carboxylic acid (2.82 g.)

Workup

  1. additionThe solution was added to the above solution
  2. stirringstirred at -15° to -10° C. for 1.5 hours
  3. customThe ethyl acetate layer was separated
  4. extractionextracted with aqueous solution of sodium bicarbonate
  5. extractionThe aqueous extract
  6. extractionextracted with ethyl acetate
  7. extractionThe ethyl acetate extract
  8. washwas washed with water
  9. dry with materialdried over magnesium sulfate
  10. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-c0c7e67bceb54860bcda9b9fd32322a7
Source dataset
uspto-grants-1984_01
Patent number
US04427674

Reaction notes

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