Methanol → ethyl 8-carbamoyl-6-(3-fluoro-4-methoxyphenyl)-9H-carbazole-2-carboxylate

Participants

Reaction Conditions

Reaction Steps

A 250 ml pressure flask was loaded with ethyl 6-bromo-8-carbamoyl-9H-carbazole-2-carboxylate (1.39 g, 3.85 mmol, Example 58C), Pd(Ph3P)4 (280 mg, 0.242 mmol), 2-(3-fluoro-4-methoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.30 g, 5.16 mmol), aqueous Na2CO3 (4.2 ml, 8.40 mmol), MeOH (21.00 ml) and Toluene (42 ml), flushed with nitrogen, sealed and heated to 105° C. for 4 hours in an oil bath. The reaction mixture was filtered and the collected solid washed with water. The filtrate was acidified with KHSO4 (1M solution in water) and extracted with dichloromethane. The organic layer was washed with brine, dried over MgSO4 and concentrated. The MgSO4 was washed with THF and a MeOH+CH2Cl2 mixture. All wash liquids, the extracted product and the collected solid residue were combined to give 1.95 g crude ethyl 8-carbamoyl-6-(3-fluoro-4-methoxyphenyl)-9H-carbazole-2-carboxylate. (estimated purity ˜75%). The crude product was used without further purification in the next reaction. MS (ESI) m/e−405 consistent with [M−H]− of product. HPLC retention time 2.13 min. (PHENOMENEX® Luna C18 S10, 3.0×50 mm column, 3 min gradient, 0-100% B, 4 mL/min. Solvent A: 5% CH3CN—95% H2O—10 mM NH4OAc; Solvent B: 95% CH3CN—5% H2O—10 mM NH4OAc), then isocratic at 100% B.

Provenance & Evidence