Toluene → 4-(4-Morpholino-3-nitrophenyl)morpholine

HRID 1431274Notes

Reaction equation

HRID 1431274 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)=[C:4]([N+:14]([O-:16])=[O:15])[CH:3]=1.[NH:17]1[CH2:22][CH2:21][O:20][CH2:19][CH2:18]1.C1(C)C=CC=CC=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.CC(C)([O-])C.[Na+]>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]>[N+:14]([C:4]1[CH:3]=[C:2]([N:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)[CH:7]=[CH:6][C:5]=1[N:8]1[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1)([O-:16])=[O:15]

Participants

7

Reactant 5

HCID 1140TolueneHCID 8083MorpholineHCID 83701685-Bromo-2-morpholinonitrobenzeneHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxide

Product 1

HCID 596314194-(4-Morpholino-3-nitrophenyl)morpholine

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Procedure

4-(4-Bromo-2-nitrophenyl)morpholine (500 mg, 1741 μmol) and morpholine (303 μL, 3483 μmol) were dissolved in toluene (71047 μL, 666992 μmol). To the stirred mixture was added X-Phos (125 mg, 261 μmol), sodium tert-butoxide (335 mg, 3483 μmol) and tris(dibenzylideneacetone)dipalladium (o) (112 mg, 122 μmol) in one portion. The reaction was heated to reflux for 2 h. After this time TLC and LC/MS show desired product. The reaction was cooled to rt and evaporated in vacuo. The residue was taken up in EtOAc (80 mL) and washed with satd aq. sodium bicarbonate solution (40 mL) and brine (40 mL). The separated organic layer was dried over magnesium sulfate, filtered and evaporated in vacuo. Column chromatography (hexanes:EtOAc, 1:0 to 1:2) gave desired product.

Workup

  1. temperatureThe reaction was heated
  2. temperatureto reflux for 2 h

Sources & evidence

ORD record
ord-0c1d686c6e4d4942920180923d648427
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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