Pyridine → HCID 86701022, compound

HRID 1855585Notes

Reaction equation

HRID 1855585 reaction equation
O(S(C(F)(F)F)(=O)=O)S(C(F)(F)F)(=O)=O.[CH2:16]([O:23][N:24]1[C:30](=[O:31])[N:29]2[CH2:32][C@H:25]1[CH2:26][CH2:27][C@H:28]2[C:33]([NH:35][NH:36][C:37](=[O:49])[CH2:38][CH2:39][N:40]([CH3:48])[C:41](=[O:47])[O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=O)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.N1C=CC=CC=1.C([O-])(O)=O.[Na+]>C(Cl)Cl>[CH2:16]([O:23][N:24]1[C:30](=[O:31])[N:29]2[CH2:32][C@H:25]1[CH2:26][CH2:27][C@H:28]2[C:33]1[O:49][C:37]([CH2:38][CH2:39][N:40]([CH3:48])[C:41](=[O:47])[O:42][C:43]([CH3:44])([CH3:45])[CH3:46])=[N:36][N:35]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

6

Reactant 4

HCID 1049PyridineHCID 67749Trifluoromethanesulfonic anhydrideHCID 516892Sodium BicarbonateHCID 86701021HCID 86701021, compound

Product 1

HCID 86701022HCID 86701022, compoundYield 51.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Tf2O (7.2 mL, 0.0423 mol) was added slowly, drop-wise to a −78° C. solution of tert-butyl 3-(2-((2S,5R)-6-(benzyloxy)-7-oxo-1,6-diaza-bicyclo[3.2.1]octane-2-carbonyl)hydrazinyl)-3-oxopropyl(methyl)carbamate (6.7 g, 14.1 mmol) and pyridine (9.1 mL, 0.113 mol) in dry DCM (110 mL). The reaction mixture was allowed to warm to 0° C. then was stirred at 0° C. for 3 hrs. Aqueous NaHCO3 was added at 0° C. very slowly. The organic layer was separated and the water layer was washed with DCM (3×). The combined organic layer was dried over Na2SO4, and concentrated. The crude product was purified by reverse-phase biotage (water/acetonitrile gradient) to afford tert-butyl 2-(5-((2S,5R)-6-(benzyloxy)-7-oxo-1,6-diaza-bicyclo[3.2.1]octan-2-yl)-1,3,4-oxadiazol-2-yl)ethyl(methyl)carbamate (3.3 g, 51%) as a light yellow solid. ESI-MS (EI+, m/z): 458.0 [M+H]+; 1H NMR (500 MHz, CDCl3): δ 7.45-7.36 (m, 5H), 5.09 (d, J=11.5 Hz, 1H), 4.94 (d, J=11.5 Hz, 1H), 4.71 (t, J=4.5 Hz, 1H), 3.67-3.59 (m, 2H), 3.37 (s, 1H), 3.31 (t, J=6.5 Hz, 2H), 2.94-2.86 (m, 2H), 2.82 (s, 3H), 2.32-2.28 (m, 2H), 2.15-2.12 (m, 1H), 2.00-1.95 (m, 1H), 1.45 (s, 9H).

Workup

  1. customdrop-wise to a −78° C.
  2. customThe organic layer was separated
  3. washthe water layer was washed with DCM (3×)
  4. dry with materialThe combined organic layer was dried over Na2SO4
  5. concentrationconcentrated
  6. customThe crude product was purified by reverse-phase biotage (water/acetonitrile gradient)

Sources & evidence

ORD record
ord-207e29f551cb414796bda4e3f2ec3596
Source dataset
uspto-grants-2015_02
Patent number
US08962844B2

Reaction notes

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