Sodium Carbonate → Benzoic acid, 5-[[5-cyclopropyl-2-(4-fluorophenyl)-3-[(methylamino)carbonyl]-6-benzofuranyl](methylsulfonyl)amino]-2-nitro-, methyl ester

Participants

Reaction Conditions

Reaction Steps

A mixture of 55.0 g (123 mmol) of 5-cyclopropyl-2-(4-fluorophenyl)-N-methyl-6-(methylsulfonamido)benzofuran-3-carboxamide, 36.7 g (184 mmol) of methyl 5-fluoro-2-nitrobenzoate, and 39.1 g (369 mmol) of sodium carbonate in 400 mL of DMF was heated to 70° C. with vigorous stirring. After 72 hours LCMS indicated nearly complete reaction. The mixture was cooled to RT, diluted with 300 mL of EtOAc, and filtered through a bed of celite to remove solids. The filter cake was washed with EtOAc until the filtrate ran colorless which gave a total filtrate volume of 1.2 L. The filtrate was transferred to a separatory funnel, partitioned with 1.4 L of 5% aqueous NaCl, and the phases separated. The aqueous solution was extracted with two additional 300 mL portions of EtOAc. The combined EtOAc solutions were washed with 95% aqueous NaCl (2×), saturated aqueous NaCl (1×), dried over sodium sulfate and concentrated to approximately 200 mL by rotary evaporation. At this point a solid began to crystallize. The suspension was diluted with 200 mL of DCM and the suspension stirred overnight. The suspension was then cooled in an ice water bath for 2 hours and the solid collected by vacuum filtration. The filter cake was washed twice with cold 1:1 EtOAc/DCM, suction air dried for 30 minutes and then dried in vacuo overnight to afford 59.6 g (83%) of methyl 5-(N-(5-cyclopropyl-2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-6-yl)methylsulfonamido)-2-nitrobenzoate as a light yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.52 (q, J=4.42 Hz, 1H) 8.13 (d, J=9.07 Hz, 1H) 8.08 (s, 1H) 7.93-8.01 (m, 2H) 7.57 (d, J=2.63 Hz, 1H) 7.53 (dd, J=9.07, 2.73 Hz, 1H) 7.38-7.46 (m, 2H) 7.29 (s, 1H) 3.83 (s, 3H) 3.60 (s, 3H) 2.85 (d, J=4.59 Hz, 3H) 1.87-2.04 (m, 1H) 0.87 (m, 2H) 0.73 (m, 1H) 0.46 (m, 1H). LCMS(ESI): 582 (M+H+).

Provenance & Evidence