N,N'-Dimethylethylenediamine → methyl 2-amino-9-methyl-6,7-dihydro-5H-benzo[7]annulene-8-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a solution of (E)-methyl 2-bromo-9-methyl-6,7-dihydro-5H-benzo[7]annulene-8-carboxylate from step B2 of preparation B (500 mg, 1.694 mmol) in dioxane (5 mL) was added 2,2,2-trifluoroacetamide (1.92 g, 16.94 mmol), copper(I) iodide (323 mg, 1.69 mmol), N1,N2-dimethylethane-1,2-diamine (448 mg, 5.08 mmol) and potassium carbonate (702 mg, 5.08 mmol). The mixture was heated in a microwave reactor at 120° C. for 2 h and 15 min. Then water (3 mL), MeOH (3 mL), and potassium carbonate (1 g) were added. The mixture was stirred at rt for 16 h. The mixture was concentrated, the residue was diluted with water (50 mL), and the mixture was extracted with EtOAc. The organic layers were combined, and concentrated. The residue was purified by silica gel column chromatography (hexanes-50% EtOAc) to afford methyl 2-amino-9-methyl-6,7-dihydro-5H-benzo[7]annulene-8-carboxylate (260 mg, 1.12 mmol, 66% yield). 1H NMR (400 MHz, chloroform-d) δ 6.96 (d, J=8.0 Hz, 1H), 6.65 (d, J=2.3 Hz, 1H), 6.58 (dd, J=7.8, 2.5 Hz, 1H), 3.80 (s, 3H), 3.62 (br. s., 2H), 2.46 (t, J=6.9 Hz, 2H), 2.37 (s, 3H), 2.17-2.01 (m, 4H).

Provenance & Evidence