Lawesson's reagent → tert-butyl ((5-((2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octan-2-yl)-1,3,4-thiadiazol-2-yl)methyl)carbamate

HRID 870854Notes

Reaction equation

HRID 870854 reaction equation
COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:10])=CC=1.[CH2:23]([O:30][N:31]1[C:37](=[O:38])[N:36]2[CH2:39][C@H:32]1[CH2:33][CH2:34][C@H:35]2[C:40]([NH:42][NH:43][C:44](=O)[CH2:45][NH:46][C:47](=[O:53])[O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=O)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C([O-])(O)=O.[Na+]>C1COCC1>[CH2:23]([O:30][N:31]1[C:37](=[O:38])[N:36]2[CH2:39][C@H:32]1[CH2:33][CH2:34][C@H:35]2[C:40]1[S:10][C:44]([CH2:45][NH:46][C:47](=[O:53])[O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[N:43][N:42]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1

Participants

5

Reactant 3

HCID 87949Lawesson's reagentHCID 516892Sodium BicarbonateHCID 86701397tert-butyl (2-(2-((2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carbonyl)hydrazinyl)-2-oxoethyl)carbamate

Product 1

HCID 86701398tert-butyl ((5-((2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octan-2-yl)-1,3,4-thiadiazol-2-yl)methyl)carbamateYield 46.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

Lawesson's reagent (0.68 g, 1.68 mol) was added to a solution of tert-butyl 2-(2-((2S,5R)-6-(benzyloxy)-7-oxo-1,6-diaza-bicyclo[3.2.1]octane-2-carbonyl)hydrazinyl)-2-oxoethylcarbamate (0.50 g, 1.12 mmol) in THF (30 mL). The reaction mixture was heated at 70° C. for 0.5 h. The solution was cooled down to rt and saturated NaHCO3 was added. The organic layer was separated and the aqueous layer was exacted with EtOAc (2×). The combined organic layer was dried over Na2SO4, and concentrated. The crude sample was dissolved in THF (100 mL), and Hg(OAc)2 (1.68 g) was added. The mixture was stirred at rt overnight, filtered and concentrated. The residue was dissolved in EtOAc (100 mL), stirred for 30 min, filtered and concentrated. The crude material was purified by silica gel column chromatography (20% to 50% EtOAc/petroleum ether) to give tert-butyl ((5-((2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octan-2-yl)-1,3,4-thiadiazol-2-yl)methyl)carbamate (230 mg, 45%) as a white solid. ESI-MS (EI+, m/z): 446.2 [M+H]+.

Workup

  1. temperatureThe solution was cooled down to rt
  2. customThe organic layer was separated
  3. dry with materialThe combined organic layer was dried over Na2SO4
  4. concentrationconcentrated
  5. dissolutionThe crude sample was dissolved in THF (100 mL)
  6. additionHg(OAc)2 (1.68 g) was added
  7. filtrationfiltered
  8. concentrationconcentrated
  9. dissolutionThe residue was dissolved in EtOAc (100 mL)
  10. stirringstirred for 30 min
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe crude material was purified by silica gel column chromatography (20% to 50% EtOAc/petroleum ether)

Sources & evidence

ORD record
ord-f3d16d804816439fa9503dc4065aae0b
Source dataset
uspto-grants-2015_03
Patent number
US08969570B2

Reaction notes

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