Morpholine → 4-(5-Morpholino-3-nitropyridin-2-yl)morpholine

HRID 1431379Notes

Reaction equation

HRID 1431379 reaction equation
Cl[C:2]1[CH:3]=[C:4]([N+:14]([O-:16])=[O:15])[C:5]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)=[N:6][CH:7]=1.[NH:17]1[CH2:22][CH2:21][O:20][CH2:19][CH2:18]1.C1(P(C2CCCCC2)C2(C(C)C)CC(C(C)C)=CC(C(C)C)=C2C2C=CC=CC=2)CCCCC1.CC(C)([O-])C.[Na+]>C1(C)C=CC=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]>[O:11]1[CH2:12][CH2:13][N:8]([C:5]2[N:6]=[CH:7][C:2]([N:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)=[CH:3][C:4]=2[N+:14]([O-:16])=[O:15])[CH2:9][CH2:10]1

Participants

7

Reactant 4

HCID 8083MorpholineHCID 23676156Sodium t-butoxideHCID 596312064-(5-Chloro-3-nitropyridin-2-yl)morpholineHCID 672859322-Dicyclohexylphosphino-2,4,6-triisopropylbiphenyl

Product 1

HCID 596312774-(5-Morpholino-3-nitropyridin-2-yl)morpholine

Reagents, catalysts & solvents 2

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 1140TolueneSolvent

Procedure

To a stirred solution of 4-(5-chloro-3-nitropyridin-2-yl)morpholine (2.48 g, 10 mmol; described herein) in toluene (190 mL) were sequentially added morpholine (1.8 mL, 20 mmol), tris(dibenzylideneacetone)dipalladium(o) (0.65 g, 0.71 mmol), 2-(dicyclohexylphosphino)-2,4,6,-tri-i-propyl-1,1-biphenyl (0.73 g, 1.5 mmol), and sodium tert-butoxide (2.0 g, 20 mmol). The reaction was heated to reflux overnight, cooled to rt, and concentrated. The resulting residue was taken up in EtOAc, washed with satd aq. sodium bicarbonate solution and brine, and the organic layer dried (magnesium sulfate) and concentrated. Column chromatography afforded 4-(6-morpholino-5-nitropyridin-3-yl)morpholine as a red oil. Mass Spectrum (ESI) m/e=295.1 (M+1).

Workup

  1. temperatureThe reaction was heated
  2. temperatureto reflux overnight
  3. concentrationconcentrated
  4. washwashed with satd aq. sodium bicarbonate solution and brine
  5. dry with materialthe organic layer dried (magnesium sulfate)
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-131aa12eec73447c943a8e72586d910e
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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