Cesium carbonate → 3-{[6-(Azetidin-1-ylcarbonyl)pyridin-3-yl]oxy}-5-[(phenylmethyl)oxy]benzoic acid

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Reaction Steps

A mixture of methyl 3-hydroxy-5-phenylmethoxy-benzoate (CAS no. 54915-31-0) (5.16 g, 20 mmol), azetidin-1-yl-(5-bromopyridin-2-yl)methanone (CAS no. 845306-16-3, Intermediate 34) (5.3 g, 22 mmol), caesium carbonate (19.6 g, 60 mmol) and tris(triphenylphosphine)copper bromide (CAS no. 15709-74-7) (3.73 g, 4 mmol) in DMA (100 mL) was stirred at 160° C. for 6 hours. The DMA was evaporated under reduced pressure and the residue was dissolved in water (200 mL), washed with ethyl acetate (3×50 mL), acidified with 2N hydrochloric acid and extracted with ethyl acetate (3×100 mL). The organic layer washed with water (2×20 mL) and brine (20 mL), dried (MgSO4) and the solvent removed under reduced pressure to afford the product (6.18 g, 76%). 1H NMR δ (400 MHz, CDCl3) 2.29 (s, 2H), 4.20 (s, 2H), 4.64 (s, 2H), 5.04 (s, 2H), 6.83 (s, 1H), 7.22-7.44 (m, 7H), 7.49 (s, 1H), 7.79-8.63 (m, 2H); m/z 405 (M+H)+.

Provenance & Evidence