Cesium carbonate → HCID 89813063, compound

Participants

Reaction Conditions

Reaction Steps

To a mixture of 4-bromo-2-{[(2,5-dimethoxy-benzyl)-ethoxycarbonylmethyl-amino]-methyl}-benzoic acid ethyl ester (3.44 g, 6.96 mmol) and 2-chloro-4-fluorophenol (2.04 g, 13.9 mmol) in NMP (6.8 mL) was added Cs2CO3 (4.53 g, 13.9 mmol). The resultant mixture was degassed and re-filled with N2 gas prior to the addition of 2,2,6,6-tetramethyl-heptane-3,5-dione (128 mg, 0.70 mmol) and Cu(I)Cl (344 mg, 3.48 mmol). It was de-gassed and filled with N2 gas again. The resultant mixture was heated in a 130° C. oil bath for 24 h. Reaction mixture was filteredthrough a pad of celite and washed with EtOAc until no UV active spot was detected from the filtrate. Filtrate was washed with 1 N HCl (100 mL and 50 mL), water and brine. It was dried over MgSO4, filtered and concentrated. Crude product was purified by silica gel chromatography, eluting with CH2Cl2, to provide the title compound 2.07 g (3.70 mmol) in 44% yield. 1H NMR (200 MHz) in CDCl3, δ ppm: 7.80 (d, J=8.4 Hz, 1H), 7.38 (d, J=2.6 Hz, 1H), 7.20 (m, 1H), 7.03 (m, 3H), 6.73 (dd, J=8.4, 2.6 Hz, 1H), 6.38 (m, 2H), 4.29 (q, J=7.2 Hz, 2H), 4.18 (s, 2H), 4.11 (q, J=7.0 Hz, 2H), 3.79 (s, 3H), 3.72 (s, 3H), 3.70 (s, 2H), 3.28 (s, 2H), 1.4-1.2 (m, 6H).

Provenance & Evidence