Trifluoromethanesulfonic acid → (4-nitrobenzyl) (1S,5R,6S)-6-[(1R)-1-hydroxyethyl]-2-[7-(pyridin-3-yl)carbonylimidazo[5,1-b]thiazol-2-yl]-1-methylcarbapen-2-em-3-carboxylate

HRID 1072352Notes

Reaction equation

HRID 1072352 reaction equation
C(N(CC)C(C)C)(C)C.[OH:10][C@@H:11]([C@H:13]1[C:34](=[O:35])[N:15]2[C@@H:16]([C:21]([O:23][CH2:24][C:25]3[CH:30]=[CH:29][C:28]([N+:31]([O-:33])=[O:32])=[CH:27][CH:26]=3)=[O:22])[C:17](=O)[C@H:18]([CH3:19])[C@H:14]12)[CH3:12].FC(F)(F)S(O)(=O)=O.O1C=CC=C1P(C1OC=CC=1)C1OC=CC=1.[N:60]1[CH:65]=[CH:64][CH:63]=[C:62]([C:66]([C:68]2[N:69]=[CH:70][N:71]3[CH:75]=[C:74]([Sn](CCCC)(CCCC)CCCC)[S:73][C:72]=23)=[O:67])[CH:61]=1.C(=O)(O)[O-].[Na+]>C(#N)C.[Cl-].[Zn+2].[Cl-].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C(OCC)(=O)C>[OH:10][C@@H:11]([C@H:13]1[C:34](=[O:35])[N:15]2[C:16]([C:21]([O:23][CH2:24][C:25]3[CH:30]=[CH:29][C:28]([N+:31]([O-:33])=[O:32])=[CH:27][CH:26]=3)=[O:22])=[C:17]([C:74]3[S:73][C:72]4=[C:68]([C:66]([C:62]5[CH:61]=[N:60][CH:65]=[CH:64][CH:63]=5)=[O:67])[N:69]=[CH:70][N:71]4[CH:75]=3)[C@H:18]([CH3:19])[C@H:14]12)[CH3:12]

Participants

11

Reactant 6

HCID 62406Trifluoromethanesulfonic acidHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 521585Tris(furan-2-yl)phosphaneHCID 13504349p-nitrobenzyl (1R,3R,5R,6S)-6-[(R)-1-hydroxyethyl]-2-oxo-1-methylcarbapenam-3-carboxylateHCID 223903847-(Pyridin-3-yl)carbonyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole

Product 1

HCID 68934911(4-nitrobenzyl) (1S,5R,6S)-6-[(1R)-1-hydroxyethyl]-2-[7-(pyridin-3-yl)carbonylimidazo[5,1-b]thiazol-2-yl]-1-methylcarbapen-2-em-3-carboxylateYield 51.7%

Reagents, catalysts & solvents 4

HCID 3007855ZincchlorideCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

Under an argon atmosphere at −30° C., N,N-diisopropylethylamine (0.343 ml) was added dropwise to a solution of 474 mg of 4-nitrobenzyl (1R,3R,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-oxo-1-carbapenam-3-carboxylate in 13 ml of dry acetonitrile, and 0.218 ml of anhydrous trifluoromethanesulfonic acid was then added dropwise thereto. The mixture was stirred at that temperature for 30 min. Ethyl acetate (30 ml) was then added thereto, followed by washing with semisaturated brine, a mixed solution (pH 1.1) composed of semisaturated brine and a 1 N aqueous hydrochloric acid solution, a mixed solution (pH 8.9) composed of semisaturated brine and a saturated aqueous sodium bicarbonate solution, and semisaturated brine in that order. The organic layer was then dried over anhydrous magnesium sulfate and was filtered. The solvent was removed by distillation under the reduced pressure. The residue was dissolved in 6 ml of dry N-methylpyrrolidinone to prepare a solution. Tri-2-furylphosphine (37 mg), 343 mg of zinc chloride, 37 mg of tris(dibenzylideneacetone)dipalladium(0), and 712 mg of 7-(pyridin-3-yl)carbonyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole were added to the solution, and the mixture was stirred at 50° C. under an argon atmosphere for 2 hr. Ethyl acetate (30 ml) and 15 ml of a semisaturated aqueous sodium bicarbonate solution were added to the reaction solution, the mixture was stirred, and the insolubles were removed by filtration. The organic layer was separated from the filtrate, was washed three times with 20 ml of semisaturated brine, and was dried over anhydrous magnesium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by column chromatography on silica gel (dichloromethane:methanol=20:1 →10:1) to give 388 mg of 4-nitrobenzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-[7-(pyridin-3-yl)carbonylimidazo[5,1-b]thiazol-2-yl]-1-carbapen-2-em-3-carboxylate.

Workup

  1. additionwas then added dropwise
  2. washby washing with semisaturated brine
  3. dry with materialThe organic layer was then dried over anhydrous magnesium sulfate
  4. filtrationwas filtered
  5. customThe solvent was removed by distillation under the reduced pressure
  6. dissolutionThe residue was dissolved in 6 ml of dry N-methylpyrrolidinone
  7. customto prepare a solution
  8. stirringthe mixture was stirred at 50° C. under an argon atmosphere for 2 hr
  9. stirringthe mixture was stirred
  10. customthe insolubles were removed by filtration
  11. customThe organic layer was separated from the filtrate
  12. washwas washed three times with 20 ml of semisaturated brine
  13. dry with materialwas dried over anhydrous magnesium sulfate
  14. customThe solvent was removed by distillation under the reduced pressure
  15. customthe residue was purified by column chromatography on silica gel (dichloromethane:methanol=20:1 →10:1)

Sources & evidence

ORD record
ord-a4c5a509557b40178947052e2e28fb6a
Source dataset
uspto-grants-2005_06
Patent number
US06908913B2

Reaction notes

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