Chlorotrimethylsilane → HCID 86686453, compound

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of 1-(pentan-2-yl)-1H-indol-5-yl isopropylcarbamate (11) (5.752 g, 19.9 mmol, 1.0 equiv.) in Et2O (143 mL) and THF (48 mL) was added TMEDA (4.19 mL, 27.9 mmol, 1.4 equiv.), and the solution was cooled to 0° C. Then, a solution of TBSOTf (5.50 mL, 23.9 mmol, 1.2 equiv.) in n-pentane (16 mL) was added, and the reaction mixture was left to stir for 5 minutes at 0° C., at which point the ice bath was removed and the reaction was stirred for 45 additional minutes. TMEDA (8.97 mL, 59.8 mmol, 3.0 equiv.) was added and the mixture was cooled to −78° C., followed by the slow addition of n-BuLi (2.5 M in hexanes, 23.9 mL, 59.8 mmol, 3.0 equiv.) over 10 minutes. The reaction mixture was stirred at −78° C. for 3 h before chlorotrimethylsilane (TMSCl, 17.4 mL, 140 mmol, 7.0 equiv.) was added slowly over 15 minutes. The reaction mixture was stirred at −78° C. for an additional 1 h. The reaction mixture was quenched with 4 mL of MeOH, followed by 200 mL of 2 M hydrochloric acid, and allowed to warm to room temperature over 1 h with vigorous stirring. Diethylether (100 mL) was added, and the organic phase was separated. The organic phase was washed with 100 mL of water, 100 mL of brine, dried over MgSO4 and concentrated. The crude material was purified via column chromatography (hexane:EtOAc, (gradient of 19:1→15:1→9:1, v/v)) to give 4-(trimethylsilyl)-1-(pentan-2-yl)-1H-indol-5-yl isopropylcarbamate (22) as a very viscous colorless liquid (6.15 g, 86%). 1H NMR (500 MHz, CDCl3) δ7.34 (d, J=8.8 Hz, 1H), 7.21 (d, J=3.3 Hz, 1H), 6.91 (d, J=8.8 Hz, 1H), 6.66 (d, J=3.2 Hz, 1H), 4.75 (d, J=8.0 Hz, 1H), 4.46 (m, 1H), 3.94 (m, 1H), 1.87 (m, 1H), 1.76 (m, 1H), 1.47 (d, J=6.8 Hz, 3H), 1.30-1.15 (m, 8H), 0.88 (t, J=7.4 Hz, 3H), 0.41 (s, 9H).

Provenance & Evidence