4-Benzyl-2-(4-bromo-phenyl)-morpholine → 4-Benzyl-2-[4-(2,6-dichloro-benzyl)-phenyl]-morpholine

HRID 920552Notes

Reaction equation

HRID 920552 reaction equation
[Cl-].[Cl:2][C:3]1[CH:10]=[CH:9][CH:8]=[C:7]([Cl:11])[C:4]=1[CH2:5][Zn+].[CH2:12]([N:19]1[CH2:24][CH:23]([C:25]2[CH:30]=[CH:29][C:28](Br)=[CH:27][CH:26]=2)[O:22][CH2:21][CH2:20]1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>C1COCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:12]([N:19]1[CH2:20][CH2:21][O:22][CH:23]([C:25]2[CH:30]=[CH:29][C:28]([CH2:5][C:4]3[C:3]([Cl:2])=[CH:10][CH:9]=[CH:8][C:7]=3[Cl:11])=[CH:27][CH:26]=2)[CH2:24]1)[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1

Participants

5

Reactant 2

HCID 580978794-Benzyl-2-(4-bromo-phenyl)-morpholineHCID 178478101HCID 178478101, compound

Product 1

HCID 670325884-Benzyl-2-[4-(2,6-dichloro-benzyl)-phenyl]-morpholineYield 94%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of 2,6-dichlorobenzylzinc chloride (7.95 mL; 0.50 mol/l in THF; 3.97 mmol) and tetrakis(triphenylphosphine)palladium(0) (83.48 mg; 0.07 mmol) in THF (25 mL) was added 4-benzyl-6-(4-bromo-phenyl)-morpholine (1.20 g; 3.61 mmol). The resulting mixture was stirred at RT for 2 hours, and subsequently heated under reflux, for 2 h. After cooling to RT the mixture was concentrated in vacuo. The residue was partitioned between 5% aqueous NaHCO3 and EtOAc. The organic layer was dried (Na2SO4), filtered, and concentrated in vacuo. The residue was purified by column chromatography (SiO2, Et2O:hexanes 1:1) to afford 4-benzyl-2-[4-(2,6-dichloro-benzyl)-phenyl]-morpholine (1.40 g).

Workup

  1. temperaturesubsequently heated
  2. temperatureunder reflux, for 2 h
  3. temperatureAfter cooling to RT the mixture
  4. concentrationwas concentrated in vacuo
  5. customThe residue was partitioned between 5% aqueous NaHCO3 and EtOAc
  6. dry with materialThe organic layer was dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by column chromatography (SiO2, Et2O:hexanes 1:1)

Sources & evidence

ORD record
ord-634a07f6e2df4df185150c5cfd33bcc7
Source dataset
uspto-grants-2016_03
Patent number
US09273017B2

Reaction notes

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