4-nitrobenzyl(5R)-6-[(acetyloxy)([1,3]thiazolo[3,2-a]benzimidazol-6-yl)methyl]-6-bromo-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate → (5R,6Z)-7-oxo-6-([1,3]thiazolo[3,2-a]benzimidazol-6-ylmethylene)-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid

HRID 638901Notes

Reaction equation

HRID 638901 reaction equation
C(O[CH:5]([C:28]1[CH:29]=[CH:30][C:31]2[N:35]=[C:34]3[S:36][CH:37]=[CH:38][N:33]3[C:32]=2[CH:39]=1)[C:6]1(Br)[C:12](=[O:13])[N:11]2[C@@H:7]1[S:8][CH:9]=[C:10]2[C:14]([O:16]CC1C=CC([N+]([O-])=O)=CC=1)=[O:15])(=O)C.[H][H]>C1COCC1.P([O-])([O-])([O-])=O>[O:13]=[C:12]1[N:11]2[C@H:7]([S:8][CH:9]=[C:10]2[C:14]([OH:16])=[O:15])/[C:6]/1=[CH:5]\[C:28]1[CH:29]=[CH:30][C:31]2[N:35]=[C:34]3[S:36][CH:37]=[CH:38][N:33]3[C:32]=2[CH:39]=1

Participants

5

Reactant 2

HCID 696085974-nitrobenzyl(5R)-6-[(acetyloxy)([1,3]thiazolo[3,2-a]benzimidazol-6-yl)methyl]-6-bromo-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylateHCID 178418361HCID 178418361, compound

Product 1

HCID 10339549(5R,6Z)-7-oxo-6-([1,3]thiazolo[3,2-a]benzimidazol-6-ylmethylene)-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acidYield 9.3%

Reagents, catalysts & solvents 2

HCID 1061PhosphateSolventHCID 8028TetrahydrofuranSolvent

Procedure

4-nitrobenzyl (5R)-6-[(acetyloxy)([1,3]thiazolo[3,2-a]benzimidazol-6-yl)methyl]-6-bromo-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (630 mg, 1 mmol) was suspended in 20 ml THF and 20 ml pH=6.5 aqueous phosphate buffer. The mixture was then subjected to 45 psi hydrogen for two hours. Then it was filtered through a pad of celite and concentrated in vacuo to remove most of the THF. The solution was then cooled to zero degree and basified to pH=8 with 1 N sodium hydroxide. Then it was purified via reverse phase HPLC using 1 liter of water followed by 5%-25% acetonitrile and water. Water was then removed through concentrate in vacuo and 33 mg of product (Yield 8%) was collected. MP: >250° C.; H-NMR (D2O): ε 6.89 (m, 8H), 5.22 (s, 2H), 5.02 (s, 2H), 4.81 (s, 2H).

Workup

  1. filtrationThen it was filtered through a pad of celite
  2. concentrationconcentrated in vacuo
  3. customto remove most of the THF
  4. temperatureThe solution was then cooled to zero degree and basified to pH=8 with 1 N sodium hydroxide
  5. customThen it was purified via reverse phase
  6. customWater was then removed

Sources & evidence

ORD record
ord-727fcd9f51a3464b82e62fc33e5e574d
Source dataset
uspto-grants-2010_04
Patent number
US07691842B2

Reaction notes

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