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

HRID 1620103

Reaction equation

HRID 1620103 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-f27689bc3ad54f79a56637174f7502b7
Source dataset
uspto-grants-2014_07
Patent number
US08772320B2

Linked notes

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