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

HRID 1427641Notes

Reaction equation

HRID 1427641 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]([CH:46]1[CH2:51][CH2:50][N:49]([C:52]([O:54][C:55]([CH3:58])([CH3:57])[CH3:56])=[O:53])[CH2:48][CH2:47]1)=O)=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]([CH:46]2[CH2:51][CH2:50][N:49]([C:52]([O:54][C:55]([CH3:58])([CH3:57])[CH3:56])=[O:53])[CH2:48][CH2:47]2)=[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 86701015tert-butyl 4-(2-((2S,5R)-6-(benzyloxy)-7-oxo-1,6-diaza-bicyclo[3.2.1]octane-2-carbonyl)hydrazinecarbonyl)piperidine-1-carboxylate

Product 1

HCID 86701017tert-butyl 4-(5-((2S,5R)-6-(benzyloxy)-7-oxo-1,6-diaza-bicyclo[3.2.1]octan-2-yl)-1,3,4-thiadiazol-2-yl)piperidine-1-carboxylateYield 56.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

Lawesson's reagent (0.16 g, 6 mol) was added to a solution of tert-butyl 4-(2-((2S,5R)-6-(benzyloxy)-7-oxo-1,6-diaza-bicyclo[3.2.1]octane-2-carbonyl)hydrazinecarbonyl)piperidine-1-carboxylate (0.16 g, 0.319 mmol) in THF (20 mL). The reaction mixture was stirred at 70° C. for 0.5 h. The solution was cooled to room temperature and sat. 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 residue was purified by silica gel column chromatography (gradient elution 20%-50% EtOAc/petroleum ether) to give tert-butyl 4-(5-((2S,5R)-6-(benzyloxy)-7-oxo-1,6-diaza-bicyclo[3.2.1]octan-2-yl)-1,3,4-thiadiazol-2-yl)piperidine-1-carboxylate (90 mg, 50%) as a white solid. ESI-MS (EI+, m/z): 500.2 [M+H]+. 1H NMR (500 MHz, DMSO-d6): δ 7.48-7.37 (m, 5H), 4.99-4.94 (m, 2H), 4.77 (d, J=7.0 Hz, 1H), 3.99 (d, J=11 Hz, 2H), 3.69 (s, 1H), 3.39-3.35 (m, 1H), 2.88-2.85 (m, 3H), 2.68 (d, J=12 Hz, 1H), 2.44 (dd, J=7.5, 5.5 Hz, 1H), 2.05-1.96 (m, 4H), 1.79-1.77 (m, 1H), 1.62-1.55 (m, 2H), 1.40 (s, 9H).

Workup

  1. temperatureThe solution was cooled to room temperature
  2. customThe organic layer was separated
  3. dry with materialThe combined organic layer was dried over Na2SO4
  4. concentrationconcentrated
  5. customThe residue was purified by silica gel column chromatography (gradient elution 20%-50% EtOAc/petroleum ether)

Sources & evidence

ORD record
ord-d9a0ba31090d4c71900030b084e16fa3
Source dataset
uspto-grants-2015_01
Patent number
US08933233B2

Reaction notes

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