Morpholine → 4-(3-Chloro-5-nitrophenyl)morpholine

HRID 1431753Notes

Reaction equation

HRID 1431753 reaction equation
Br[C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[C:4]([Cl:11])[CH:3]=1.[NH:12]1[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1.CC(C)([O-])C.[Na+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>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].C1(C)C=CC=CC=1>[Cl:11][C:4]1[CH:3]=[C:2]([N:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=1

Participants

7

Reactant 4

HCID 8083MorpholineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 178398381-Bromo-3-chloro-5-nitrobenzeneHCID 23676156Sodium t-butoxide

Product 1

HCID 596310694-(3-Chloro-5-nitrophenyl)morpholine

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 1-bromo-3-chloro-5-nitrobenzene (4.5 g, 19.03 mmol), morpholine (1.7 mL, 19.03 mmol), sodium tert-butoxide (3.11 g, 32.4 mmol), tris(dibenzylideneacetone)dipalladium (0) (0.87 g, 0.952 mmol), XPhos (0.91 g, 1.903 mmol), and toluene (40 mL) was stirred at 100° C. under nitrogen for 2 h, then filtered through Celite and concd. The resulting residue was partitioned between EtOAc and water, and the organic phase was washed with satd aqueous sodium bicarbonate and brine, dried over magnesium sulfate, and concd. Purification by column chromatography (silica; 0-25% EtOAc in hexanes) afforded 4-(3-chloro-5-nitrophenyl)morpholine as a yellow amorphous solid. Mass Spectrum (ESI) m/e=243.0 (M+1).

Workup

  1. filtrationfiltered through Celite and concd
  2. customThe resulting residue was partitioned between EtOAc and water
  3. washthe organic phase was washed with satd aqueous sodium bicarbonate and brine
  4. dry with materialdried over magnesium sulfate, and concd
  5. customPurification by column chromatography (silica; 0-25% EtOAc in hexanes)

Sources & evidence

ORD record
ord-8959c64a12a44b6993f6d9d56403139a
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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