Methanesulfonic Acid → (6R)-7-amino-3-hydroxy-8-oxo-5-thia-1-azabicyclo[4.2.0]octane-2-carboxylic acid

HRID 1982044Notes

Reaction equation

HRID 1982044 reaction equation
[NH2:1][CH:2]1[C:13](=[O:14])[N:4]2[CH:5]([C:10]([OH:12])=[O:11])[C:6](=C)[CH2:7][S:8][C@H:3]12.CS(O)(=O)=[O:17]>CO>[NH2:1][CH:2]1[C:13](=[O:14])[N:4]2[CH:5]([C:10]([OH:12])=[O:11])[CH:6]([OH:17])[CH2:7][S:8][C@H:3]12

Participants

4

Reactant 2

HCID 6395Methanesulfonic AcidHCID 130225477-Amino-3-methylenecepham-4-carboxylic acid

Product 1

HCID 13072520(6R)-7-amino-3-hydroxy-8-oxo-5-thia-1-azabicyclo[4.2.0]octane-2-carboxylic acidYield 65%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

7-Amino-3-methylenecepham-4-carboxylic acid (107 g.) was dissolved in a solution of methanol (6.4 l.) and methanesulfonic acid (57.7 g.). Ozone was bubbled into the solution at -70° to -75° C. until the starting compound was not detected. After bubbling nitrogen gas into the resultant mixture, sodium methoxide (3.5 g.) was added to the mixture below -65° C. Sodium borohydride (56.7 g.) was added to a solution of sodium hydroxide (14.4 g.) in water (3.2 l), stirred at room temperature for 20 minutes and chilled. The oxidized reaction mixture was added to the sodium borohydride solution over 3 minutes, and stirred at -4° to 0° C. for 20 minutes. The solution was adjusted to pH 4.0 with 6N hydrochloric acid, and allowed to stand at 5° C. overnight. The precipitates were collected by filtration, washed with methanol and then dried to give 7-amino-3-hydroxycepham-4-carboxylic acid (70.8 g.).

Workup

  1. customOzone was bubbled into the solution at -70° to -75° C. until the starting compound
  2. customAfter bubbling nitrogen gas into the resultant mixture, sodium methoxide (3.5 g.)
  3. additionwas added to the mixture below -65° C
  4. additionSodium borohydride (56.7 g.) was added to a solution of sodium hydroxide (14.4 g.) in water (3.2 l)
  5. temperaturechilled
  6. additionThe oxidized reaction mixture was added to the sodium borohydride solution over 3 minutes
  7. stirringstirred at -4° to 0° C. for 20 minutes
  8. waitto stand at 5° C. overnight
  9. filtrationThe precipitates were collected by filtration
  10. washwashed with methanol
  11. customdried

Sources & evidence

ORD record
ord-bd29795795854ff5a82f10e2aeab3caf
Source dataset
uspto-grants-1986_06
Patent number
US04594446

Reaction notes

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