Cesium carbonate → Methyl {1-[(4-chlorophenyl)(phenyl)methyl]azetidin-3-yl}(3,5-difluorophenyl)acetate

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Reaction Steps

A solution of 0.042 g (0.15 mmol) of 1-[bromo(phenyl)methyl]-4-chlorobenzene, 0.028 g (0.1 mmol) of methyl azetidin-3-yl(3,5-difluorophenyl)acetate (Example 25, Step 1) and 0.298 g (0.3 mmol) of Cs2CO3 in 5 mL of acetonitrile was heated at 45° C. for 18 h. The solution was concentrated and the residue was dissolved in 5 mL of ethyl acetate. This solution was washed with 1 mL water and the aqueous layer was washed with a second aliquot of 3 mL ethyl acetate. The organic extracts were washed with brine, combined, dried over Na2SO4 and concentrated. The residue was purified by chromatography on a Waters RCM column (5 micron silica gel, 20 mm×10 cm) using a 2:1 mixture of hexane and 5:4:1 hexane-methyl tert-butyl ether-acetonitrile. Homogenous fractions were pooled and concentrated to afford the title compound. 1NMR (CDCl3) δ 2.65-2.69 (m, 1H), 2.88-2.93 (m, 1H), 3.05-3.16 (m, 2H), 3.41-3.46 (m, 1H), 3.67 (s, 3H), 3.81-3.86 (m, 1H), 4.30 (s, 1H), 6.69-6.74 (m, 1H), 6.80-6.85 (m, 2H), 7.19-7.37 (m, 9H). Mass Spectrum: m/e=442 (M+1 35Cl) and 444 (M+1 37Cl).

Provenance & Evidence