Dichloromethane → (1R)-N-Methyl-1-[3'-(methyloxy)-4-biphenylyl]-2-(4-morpholinyl)ethanamine

Temperature

100 °C

[(1R)-1-(4-Bromophenyl)-2-(4-morpholinyl)ethyl]methylamine (3.5 g, 11.7 mmol) was dissolved in a dioxane/H2O solution (140 mL, 5:2 volume ratio) at room temperature with magnetic stirring. The resulting solution was treated with 3-methoxylbenzene boronic acid (1.76 g, 12.9 mmol) followed by K2CO3 (4.85 g, 3.51 mmol) and PdCl2(dppf)2.CH2Cl2 (0.48 g, 0.59 mmol). The reaction was maintained at 100° C. for 5 h. The reaction mixture was cooled to room temperature and then filtered through celite. The filtrate was concentrated and then partitioned between EtOAc and brine. The organic layer was dried over MgSO4, and filtered. The filtrate was concentrated, and the residue was purified by silica gel chromatography (120 g Redisep column, silica, 40 um, 60 Å, 80 mL/min, A: MeOH (with 10% NEt3), B: CH2Cl2, A: 2% for 20 min, 5% for 20 min, 10% for 10 min; detection at 254 nm) to give the title compound as a yellow oil (3.3 g, 85%). MS (ES) m/e 327 [M+H]+.

1. temperatureThe reaction mixture was cooled to room temperature
2. filtrationfiltered through celite
3. concentrationThe filtrate was concentrated
4. custompartitioned between EtOAc and brine
5. dry with materialThe organic layer was dried over MgSO4
6. filtrationfiltered
7. concentrationThe filtrate was concentrated
8. customthe residue was purified by silica gel chromatography (120 g Redisep column, silica, 40 um, 60 Å, 80 mL/min
9. wait5% for 20 min
10. wait10% for 10 min

ORD record

ord-e18aa0a010874d7787a6752af4a00576

Source dataset

uspto-grants-2010_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07749998B2