Diisopropylethylamine → HCID 58386810, compound

HRID 73554Notes

Reaction equation

HRID 73554 reaction equation
[O:1]=[C:2]1[N:20]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[C@@H:5]2[CH2:6][N:7]([C:10](OCC3C=CC=CC=3)=O)[CH2:8][CH2:9][C@@H:4]2[O:3]1.O=C1N(C(OC(C)(C)C)=O)[C@@H]2CNCC[C@@H]2O1.ClC1[CH:51]=[CH:50][N:49]=[CH:48][C:47]=1[N+:52]([O-:54])=[O:53].CCN(C(C)C)C(C)C>CCO.CCOC(C)=O.CC(O)C.[Pd]>[N+:52]([C:47]1[CH:48]=[N:49][CH:50]=[CH:51][C:10]=1[N:7]1[CH2:8][CH2:9][C@@H:4]2[O:3][C:2](=[O:1])[N:20]([C:21]([O:23][C:24]([CH3:25])([CH3:26])[CH3:27])=[O:22])[C@@H:5]2[CH2:6]1)([O-:54])=[O:53]

Participants

9

Reactant 4

HCID 81531DiisopropylethylamineHCID 27357814-Chloro-3-nitropyridineHCID 58386786HCID 58386786, compoundHCID 67346906(3aR,7aS)-tert-butyl 2-oxohexahydrooxazolo[4,5-c]pyridine-3(2H)-carboxylate

Product 1

HCID 58386810HCID 58386810, compoundYield 89%

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 3776IsopropanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
75 °C

Procedure

To a solution of (3aR,7aS)-5-benzyl 3-tert-butyl 2-oxotetrahydrooxazolo[4,5-c]pyridine-3,5(2H,6H)-dicarboxylate in a mixture of EtOH and EtOAc (1:1, 0.07M) was added Pd/C (10% by weight) and the reaction was stirred under a hydrogen balloon for 15 h. The solution was then filtered through a pad of Celite and the filtrate was concentrated to dryness to give a clear oil. To a solution of (3aR,7aS)-tert-butyl 2-oxohexahydrooxazolo[4,5-c]pyridine-3(2H)-carboxylate in i-PrOH (0.12 M) was added 4-chloro-3-nitropyridine (1.2 equiv.) and DIEA (4.0 equiv.) The reaction was heated to 75° C. for 2 h, then cooled to room temperature and concentrated under vacuo. The crude mixture was diluted with EtOAc, water was added, the organic layer was extracted, washed with brine, dried with Na2SO4, and concentrated. The crude was purified via silica gel column chromatography eluting with EtOAc (100%) to yield (3aR,7aS)-tert-butyl 5-(3-nitropyridin-4-yl)-2-oxohexahydrooxazolo[4,5-c]pyridine-3(2H)-carboxylate as a yellow foam in 89% yield). LCMS (m/z): 365.1 (MH+), Rt=1.79 min.

Workup

  1. filtrationThe solution was then filtered through a pad of Celite
  2. concentrationthe filtrate was concentrated to dryness
  3. customto give a clear oil
  4. temperaturecooled to room temperature
  5. concentrationconcentrated under vacuo
  6. additionThe crude mixture was diluted with EtOAc, water
  7. additionwas added
  8. extractionthe organic layer was extracted
  9. washwashed with brine
  10. dry with materialdried with Na2SO4
  11. concentrationconcentrated
  12. customThe crude was purified via silica gel column chromatography
  13. washeluting with EtOAc (100%)

Sources & evidence

ORD record
ord-a4583c37f25f4a018a5c271a02b67059
Source dataset
uspto-grants-2014_09
Patent number
US08829193B2

Reaction notes

Loading…