Morpholine → 4-(2-methoxyphenyl)morpholine

HRID 1777144Notes

Reaction equation

HRID 1777144 reaction equation
I[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[O:8][CH3:9].[NH:10]1[CH2:15][CH2:14][O:13][CH2:12][CH2:11]1.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.C(O[Na])(C)(C)C>O1CCOCC1.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]>[CH3:9][O:8][C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[N:10]1[CH2:15][CH2:14][O:13][CH2:12][CH2:11]1

Participants

7

Reactant 4

HCID 8083MorpholineHCID 68257o-IodoanisoleHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 178418730sodium 2-methylpropan-2-olate

Product 1

HCID 106554094-(2-methoxyphenyl)morpholineYield 70%

Reagents, catalysts & solvents 2

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

Procedure

To a solution of 1-iodo-2-methoxybenzene (1 g, 4.28 mmol) in dioxane (10 mL) was added morpholine (446.8 mg, 5.12 mmol), Pd2(dba)3 (100 mg, 0.1 mmol), Xantphos (200 mg, 0.3 mmol) and t-BuONa (671 mg, 6.0 mmol). Under a N2 atmosphere the reaction mixture was heated at reflux temperature for 16 h. The solvent was then removed and the residue dissolved in ethyl acetate and washed with water. The separated organic layer was concentrated to give the crude product which was used in next step without further purification (578 mg Yield 70%). LCMS (m/z): 194.1 (M+1).

Workup

  1. temperatureUnder a N2 atmosphere the reaction mixture was heated
  2. temperatureat reflux temperature for 16 h
  3. customThe solvent was then removed
  4. dissolutionthe residue dissolved in ethyl acetate
  5. washwashed with water
  6. concentrationThe separated organic layer was concentrated

Sources & evidence

ORD record
ord-d67385388ed2462abfb5fb117b237643
Source dataset
uspto-grants-2016_02
Patent number
US09266836B2

Reaction notes

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