2-methyl-2,3,4,5-tetrahydro-1H-pyrido(4,3-b)indole → Methyl 4-((2-methyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)methyl)benzoate

Participants

Reaction Conditions

Reaction Steps

Potassium tert-butoxide (0.95 g, 8.5 mmol) was placed under argon and suspended in 1 mL of anhydrous DMF. To it was added 2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (17) (1.5 g, 8.1 mmol) dissolved in 3 mL of DMF upon which the reaction turned a deep orange in color. The reaction was stirred at room temperature for 15 min after which 4-bromomethyl-benzoic acid methyl ester (1.8 g, 8.1 mmol) was added in 1 mL of DMF along with approximately 5 mg of potassium iodide. The reaction then turned a light orange in color. The reaction was stirred at 80° C. for two hours after which the reaction was quenched by the addition of 15 mL of water. The pH was adjusted to approximately 12 with 2N NaOH and the organic products were extracted with ethyl acetate (3×15 mL). The combined organic layers were washed with water (15 mL), brine (15 mL), dried with anhydrous sodium sulfate, filtered, and concentrated in vacuo. Purification by column chromatography (0-80% gradient of ethyl acetate in hexane) afforded the title compound (1.7 g, 61%) as a yellow oil. 1H NMR (400 MHz, CD3OD): δ 7.83 (d, 2H, J=8.3 Hz), 7.33 (d, 1H, J=7.8 Hz), 7.23 (m, 3H), 7.07 (m, 1H), 6.97 (m, 1H), 4.59 (s, 2H), 4.01 (s, 2H), 3.82 (s, 3H), 2.90 (t, 2H, J=5.5 Hz), 2.84 (t, 2H, J=5.3 Hz), 2.48 (s, 3H). 13C NMR (100 MHz, MeOD): δ 167.1, 147.5, 134.9, 130.4, 129.2, 128.1, 128.0, 127.4, 120.4, 119.2, 177.7, 108.3, 108.1, 65.4, 51.0, 50.0, 40.2, 29.2, 20.3. ESI-MS (m/z): [M+H]+ 335.2 m/z.

Provenance & Evidence