Morpholine → 2-Methoxy-3-morpholino-5-nitropyridine

HRID 2406751Notes

Reaction equation

HRID 2406751 reaction equation
[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.Br[C:56]1[C:57]([O:65][CH3:66])=[N:58][CH:59]=[C:60]([N+:62]([O-:64])=[O:63])[CH:61]=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O.O1CCOCC1>[CH3:66][O:65][C:57]1[C:56]([N:1]2[CH2:6][CH2:5][O:4][CH2:3][CH2:2]2)=[CH:61][C:60]([N+:62]([O-:64])=[O:63])=[CH:59][N:58]=1

Participants

8

Reactant 4

HCID 8083MorpholineHCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 215844513-Bromo-2-methoxy-5-nitropyridine

Product 1

HCID 680279252-Methoxy-3-morpholino-5-nitropyridine

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

Morpholine (54 μl), cesium carbonate (336 mg), Pd2(dba)3 (57 mg), and Xantphos (72 mg) were added to a 1,4-dioxane (3 ml) solution containing 3-bromo-2-methoxy-5-nitropyridine (96 mg) in a nitrogen atmosphere, followed by stirring at 100° C. for 10 hours. The reaction solution was adjusted to room temperature, and water was added, followed by extraction with ethyl acetate. The resultant was washed with saturated saline and dried over anhydrous sodium sulfate, and the solvent was distilled away under reduced pressure. The obtained residue was purified by silica gel chromatography (n-hexane:ethyl acetate=4:1 to 2:1), and a yellow solid of 2-methoxy-3-morpholino-5-nitropyridine (54 mg) was thus obtained.

Workup

  1. customwas adjusted to room temperature
  2. extractionfollowed by extraction with ethyl acetate
  3. washThe resultant was washed with saturated saline
  4. dry with materialdried over anhydrous sodium sulfate
  5. distillationthe solvent was distilled away under reduced pressure
  6. customThe obtained residue was purified by silica gel chromatography (n-hexane:ethyl acetate=4:1 to 2:1)

Sources & evidence

ORD record
ord-74b750d8a68a45c69747dca36a6b76c5
Source dataset
uspto-grants-2014_08
Patent number
US08809371B2

Reaction notes

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