反应详情

A solution of 0.280 g (1 mmol) of 1-[bromo(phenyl)methyl]4-chlorobenzene, 0.120 g (0.5 mmol) of methyl azetidin-3-yl(3,5-difluorophenyl)acetate (Example 22, Step 1) and 0.12 mL (0.7 mmol) of diisopropylethylamine in 10 mL of acetonitrile was heated at 40° C. for 18 h. The solution was concentrated and the residue was dissolved in 20 mL of ethyl acetate. This solution was washed with 10 mL water and the aqueous layer was washed with a second aliquot of 20 mL ethyl acetate. The organic extracts were washed with brine, combined, and concentrated. The residue was dissolved in acetonitrile and purified by reverse phase chromatography (Waters Xterra C18, 19 mm×50 mm) using a gradient of acetonitrile-water-triethylamine (30:70:1 to 60:40:1) to afford the title compound; 1NMR (CDCl3) δ 3.74 (s, 3H), 3.88 (m, 2H), 4.24 (m, 2H), 4.55 (s, 1H), 6.70-6.86 (m, 3H), 7.21-7.43 (m, 911); Mass Spectrum: m/e=440 (M+1 35Cl) and 442 (M+1 37Cl).

1. concentrationThe solution was concentrated
2. dissolutionthe residue was dissolved in 20 mL of ethyl acetate
3. washThis solution was washed with 10 mL water
4. washthe aqueous layer was washed with a second aliquot of 20 mL ethyl acetate
5. washThe organic extracts were washed with brine
6. concentrationconcentrated
7. dissolutionThe residue was dissolved in acetonitrile
8. custompurified by reverse phase chromatography (Waters Xterra C18, 19 mm×50 mm)