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

HRID 638898Notes

Reaction equation

HRID 638898 reaction equation
C(O[CH:5]([C:28]1[CH:29]=[CH:30][C:31]2[N:35]=[C:34]3[S:36][CH2:37][CH2:38][CH2:39][N:33]3[C:32]=2[CH:40]=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>[S:36]1[C:34]2=[N:35][C:31]3[CH:30]=[CH:29][C:28](/[CH:5]=[C:6]4\[C@@H:7]5[N:11]([C:12]\4=[O:13])[C:10]([C:14]([OH:16])=[O:15])=[CH:9][S:8]5)=[CH:40][C:32]=3[N:33]2[CH2:39][CH2:38][CH2:37]1

Participants

5

Reactant 2

HCID 696087324-nitrobenzyl (5R)-6-[(acetyloxy)(3,4-dihydro-2H-[1,3]thiazino[3,2-a]benzimidazol-7-yl)methyl]-6-bromo-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylateHCID 178418361HCID 178418361, compound

Product 1

HCID 10069138(5R,6Z)-6-(3,4-dihydro-2H-[1,3]thiazino[3,2-a]benzimidazol-7-ylmethylene)-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acidYield 18.4%

Reagents, catalysts & solvents 2

HCID 1061PhosphateSolventHCID 8028TetrahydrofuranSolvent

Procedure

4-nitrobenzyl (5R)-6-[(acetyloxy)(3,4-dihydro-2H-[1,3]thiazino[3,2-a]benzimidazol-7-yl)methyl]-6-bromo-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (700 mg, 1.1 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 75 mg of product (Yield 18%) was collected. MP: >250° C., H-NMR (D2O): δ 7.08 (m, 6H), 3.70 (m, 2H), 4.05 (m, 2H), 3.13 (m, 2H), 2.22 (m, 2H); MS: 372.1 (M+H).

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-2540153fb0d7453a86b4e21e67b1db22
Source dataset
uspto-grants-2010_04
Patent number
US07691842B2

Reaction notes

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