Diketene → Benzhydryl 7-(4-bromoacetoacetamido)-3-methylthiomethyl-3-cephem-4-carboxylate

HRID 234179Notes

Reaction equation

HRID 234179 reaction equation
C=C1OC(=O)C1.BrBr.[Br:9][CH2:10][C:11](=[O:16])[CH2:12][C:13](Br)=[O:14].[NH2:17][CH:18]1[C:44](=[O:45])[N:20]2[C:21]([C:28]([O:30][CH:31]([C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)[C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)=[O:29])=[C:22]([CH2:25][S:26][CH3:27])[CH2:23][S:24][C@H:19]12.C[Si](CC(N)=O)(C)C.C(=O)(O)[O-].[Na+]>C(Cl)Cl.O>[Br:9][CH2:10][C:11](=[O:16])[CH2:12][C:13]([NH:17][CH:18]1[C:44](=[O:45])[N:20]2[C:21]([C:28]([O:30][CH:31]([C:38]3[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=3)[C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)=[O:29])=[C:22]([CH2:25][S:26][CH3:27])[CH2:23][S:24][C@H:19]12)=[O:14]

Participants

9

Reactant 6

HCID 12661DiketeneHCID 24408BromineHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 516892Sodium BicarbonateHCID 128310484-Bromo-3-oxobutanoyl bromideHCID 67712714Benzhydryl 7-amino-3-methylthiomethyl-3-cephem-4-carboxylate

Product 1

HCID 131713143Benzhydryl 7-(4-bromoacetoacetamido)-3-methylthiomethyl-3-cephem-4-carboxylate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent3×

Procedure

To a solution of diketene (1.3 ml) in methylene chloride (10 ml) was added dropwise a solution of bromine (1.24 g) in methylene chloride (10 ml) at -30° C. with stirring, and the stirring was continued at -20° C. for half an hour to prepare a solution of 4-bromoacetoacetyl bromide. This solution was added dropwise to a solution of benzhydryl 7-amino-3-methylthiomethyl-3-cephem-4-carboxylate (4.44 g) and trimethylsilylacetamide (5.46 g) in methylene chloride (100 ml) at -30° to -20° C. over a period of 5 minutes with stirring, and the stirring was continued at -10° C. for half an hour. After addition of water, the resultant mixture was adjusted to pH 7.5 with an aqueous solution of sodium bicarbonate, followed by separating out the organic layer, which was washed with water and an aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, and then evaporated to dryness to give benzhydryl 7-(4-bromoacetoacetamido)-3-methylthiomethyl-3-cephem-4-carboxylate (6.0 g).

Workup

  1. waitthe stirring was continued at -20° C. for half an hour
  2. stirringwith stirring
  3. waitthe stirring was continued at -10° C. for half an hour
  4. customby separating out the organic layer, which
  5. washwas washed with water
  6. dry with materialan aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate
  7. customevaporated to dryness

Sources & evidence

ORD record
ord-0a9d6ea8c51247bc868cc34198842330
Source dataset
uspto-grants-1997_01
Patent number
US05594132

Reaction notes

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