反应详情

温度

120 °C

Tetramethylstannane (41 μl, 0.295 mmol) was added to the intermediate from Example 1 Step H (35 mg, 0.059 mmol), Pd(PPh3)4 (5 mg, 0.04 mmol) in 3 mL DMF. The solution was then heated at 120° C. overnight under an argon atmosphere. The solution was cooled and partitioned between ethyl acetate and water. The organic phase was washed with water (3×) and brine. The solution was then dried over Na2SO4, filtered and concentrated. The residue was purified by PTLC using 6/4 hexanes/ethyl acetate mobile phase to give tert-butyl N-(4-{2-[4-methyl-4-(trifluoromethoxy)biphenyl-3-yl]ethyl}benzoyl)-β-alaninate. The tert butyl group was removed with TFA as described in EXAMPLE 1 Step I to give the title compound. 1H NMR (500 MHz, CDCl3): δ 7.73 (d, J=7.9 Hz, 2H); 7.54 (d, J=8.5 Hz, 2H); 7.36-7.33 (m, 1H); 7.31-7.23 (m, 6H); 6.81-6.76 (m, 1H); 3.80-3.75 (m, 2H); 2.99 (s, 4H); 2.77 (t, J=5.7 Hz, 2H); 2.35 (s, 3H). LCMS1 3.94 min (M+H)=472

1. temperatureThe solution was cooled
2. custompartitioned between ethyl acetate and water
3. washThe organic phase was washed with water (3×) and brine
4. dry with materialThe solution was then dried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated
7. customThe residue was purified by PTLC