Hydrogen Bromide → 7alpha-Bromo-3-methyl-3-cephem-4-carboxylic acid

HRID 257997

Reaction equation

HRID 257997 reaction equation
[CH3:1][C:2]1[CH2:11][S:10][C@@H:5]2[C@H:6](N)[C:7](=[O:8])[N:4]2[C:3]=1[C:12]([OH:14])=[O:13].C(O)C.[BrH:18].N([O-])=O.[Na+]>O>[Br:18][C@H:6]1[C:7](=[O:8])[N:4]2[C:3]([C:12]([OH:14])=[O:13])=[C:2]([CH3:1])[CH2:11][S:10][C@H:5]12

Participants

6

Reactant 4

HCID 260Hydrogen BromideHCID 702EthanolHCID 334987-Aminodeacetoxycephalosporanic acidHCID 23668193Sodium Nitrite

Product 1

HCID 152807947alpha-Bromo-3-methyl-3-cephem-4-carboxylic acidYield 75.5%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To an ice-cooled mixture of 7-ADCA (10.0 g, 0.4667 mol), ethanol (270 ml), water (83 ml) and hydrobromic acid (48%, 56.7 ml), sodium nitrite (4.67 g, 0.6769 mol) was added in small portions over 25 minutes and the mixture was stirred for 2.5 hours at ice-temperature. Ethanol was removed under reduced pressure and the residual mass was diluted with methylene chloride, washed with water. The aqueous washings were saturated with brine and re-extracted with methylene chloride. The combined organic layer was washed with brine, dried over anhydrous sodium sulfate and concentrated to give 9.8 g (75.5%) of 7α-bromo-3-methyl -3-cephem-4-carboxylic acid. This crude acid was directly used for the next step without further purification.

Workup

  1. additionwas added in small portions over 25 minutes
  2. customEthanol was removed under reduced pressure
  3. additionthe residual mass was diluted with methylene chloride
  4. washwashed with water
  5. extractionre-extracted with methylene chloride
  6. washThe combined organic layer was washed with brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-53779bcc29e147339cc0f8665c5ff7c9
Source dataset
uspto-grants-1993_11
Patent number
US05264429

Linked notes

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