Toluene → 4-(4'-Methyl-biphenyl-4-ylmethyl)-2-phenyl-morpholine

Temperature

120 °C

91 mg of 4-(4-Bromo-benzyl)-2-phenyl-morpholine was combined with 56 mg of 4-Methylphenyl boronic acid, 16 mg of tetrakis(triphenylphosphine)palladium(0), 0.92 mL of 2M sodium carbonate solution, 2.5 mL toluene and 1.23 mL ethanol. The reaction mixture was heated in a sealed tube at 120° C. overnight in an oil bath. The reaction mixture was filtered through Celite and concentrated in vacuo. The residue was diluted with 4 mL DCM and 130 mg of MP-TsOH resin (4.2 mmol/g loading) was added and the mixture agitated at room temperature overnight. The solution is filtered and the resin is then washed with 2M N3 in methanol to liberate product. The resin is washed several times with methylene chloride, concentrated in vacuo and purified by reverse phase HPLC. 18.5 mg of product was obtained as oil. ES MS m/z 344, 20% yield

1. filtrationThe reaction mixture was filtered through Celite
2. concentrationconcentrated in vacuo
3. additionThe residue was diluted with 4 mL DCM and 130 mg of MP-TsOH resin (4.2 mmol/g loading)
4. additionwas added
5. filtrationThe solution is filtered
6. washthe resin is then washed with 2M
7. washThe resin is washed several times with methylene chloride
8. concentrationconcentrated in vacuo
9. custompurified by reverse phase HPLC

ORD record

ord-1495aa064d634c04be80618b38e8383e

Source dataset

uspto-grants-2009_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07595397B2