Triethylamine → methyl 9-(4-fluorobenzyl)-2-methyl-1-oxo-4-(p-tolyl)-2,9-dihydro-1H-pyrido[3,4-b]indole-3-carboxylate

Participants

Reaction Conditions

Reaction Steps

An ice cold solution of methyl 9-(4-fluorobenzyl)-4-hydroxy-2-methyl-1-oxo-2,9-dihydro-1H-pyrido[3,4-b]indole-3-carboxylate (1.1 g, 2.89 mmol) and Et3N (2.004 ml, 14.46 mmol) in DCM (30 mL) was treated with Tf2O (0.977 ml, 5.78 mmol). After 15 min, the reaction mixture was poured into sat. aq. NaHCO3 and extracted with EtOAc. The organic phase was washed with brine, dried (MgSO4), filtered and concentrated in vacuo. The crude residue was dissolved in 1,4-Dioxane (9.57 ml)/Water (1.913 ml), treated with 4-methylphenyl boronic acid (0.550 g, 4.05 mmol) and Na2CO3 (0.920 g, 8.68 mmol) and then degassed with N2 for 5 min. Pd(PPh3)4 (0.334 g, 0.289 mmol) was added and the reaction mixture was warmed to 80° C. After 2 h, the reaction mixture was poured into sat. aq. NH4Cl and extracted with EtOAc. The organic layer was dried (MgSO4), filtered and concentrated in vacuo. the residue was purified by ISCO (0-50% EtOAc-hexanes) to afford methyl 9-(4-fluorobenzyl)-2-methyl-1-oxo-4-(p-tolyl)-2,9-dihydro-1H-pyrido[3,4-b]indole-3-carboxylate (625 mg, 1.375 mmol, 47.6% yield) as a yellow solid. 1H NMR (400 MHz, CHLOROFORM-d)=7.31 (d, J=3.9 Hz, 6H), 7.22 (none, 2H), 6.96 (s, 4H), 6.15 (s, 2H), 3.70 (s, 3H), 3.59 (s, 3H), 2.48 (s, 3H).

Provenance & Evidence