Reaction Steps
To a solution of MeLi in diethyl ether (5.1 mL, 1.6 M, 8.2 mmol, 6.0 eq.) and anhydrous and degazed THF (70 mL) was added, under an argon atmosphere and at 10° C., ketone tert-butyl 5-methoxy-3-(2-(pyridin-3-yl)acetyl)-1H-indol-1-carboxylate (1.2 g, 3.3 mmol, 1.0 eq.). The reaction mixture was stirred at 10° C. for 15 minutes and then, cooled to 0° C. and quenched with a saturated aqueous ammonium chloride solution. The mixture was extracted with ethyl acetate and the organic layer was dried over MgSO4 and evaporated under reduced pressure. To the alcohol residue taken up in toluene (70 mL) was added KHSO4 (1.1 g, 8.2 mmol) and the mixture was heated at 70° C. for 18 hours and quenched with a saturated aqueous sodium bicarbonate solution, after cooling to room temperature. The mixture was extracted with ethyl acetate and the organic layer was dried over MgSO4 and evaporated. The residue was purified by silica gel flash-column chromatography (eluent: CH2Cl2/EtOH, 99/1 to 97/3) to afford the two diastereoisomers represented herein only by the compound (59), namely the major one (E), as a yellow mering (200 mg, 56%, E/Z ratio: 80/20). TLC: Rf=0.30 (CH2Cl2/EtOH, 96/4); IR νmax (cm−1): 2925 (νC—H aliphatic); 1H RMN (DMSO, 500 MHz) δ isomere E (ppm): 2.29 (3H, s, 3H3′), 3.80 (3H, s, 5-methoxy), 6.82 (1H, dd, J6-7=8.9 Hz, J6-4=2.3 Hz, H6), 6.93 (1H, s, H1′), 7.33 (1H, d, J7-6=8.9 Hz, H7), 7.39 (2H, m, H4 et H5″), 7.59 (1H, s, H2), 7.82 (1H, d, J4″-5″=7.9 Hz, H4″), 8.40 (1H, d, J6″-5″=4.6 Hz, H6″), 8.63 (1H, s, H2″), 11.21 (1H, s, indolic H); 13C NMR (DMSO, 75.5 MHz) 8 isomere E (ppm): 18.5 (C3′), 55.9 (5-methoxy), 103.0 (C4), 111.8 (C6), 113.1 (C7), 118.1 (C3), 119.2 (C1′), 123.7 (C5″), 125.3 (C3a), 126.1 (C2), 132.7 (C7a), 134.8 (C3″), 135.1 (C2′), 136.2 (C4″), 146.8 (C6″), 150.4 (C2″), 154.4 (C5); ESI-MS: m/z 265.2 ([M+H]+); HRESI-MS: m/z 265.1340 (calcd for C17H17N2O+, 265.1341).
