Potassium bis(trimethylsilyl)amide → Methyl 3-bromo-4-{(2rs)-2-[(5-chloro-1-methyl-1h-indol-2-yl)carbonyl]heptyl}benzoate

Participants

Reaction Steps

To a cooled (−78° C.) solution of the title compound of Example 1 Step B (161 mg, 0.58 mmol) in THF (3 mL) was added KHMDS (2.30 mL, 0.5 M in toluene, 1.15 mmol). After 30 min, a solution of the title compound of Example 2 Step A (357.0 mg, 1.16 mmol) in THF (3 mL) was added, and the resultant mixture was allowed to warm slowly to room temperature over 15 h. The mixture was then quenched by addition of sat. aq. NaHCO3, and the aqueous phase was extracted with EtOAc. The organic phase was dried over anhydrous Na2SO4, and concentrated in vacuo. The crude product was taken forward without further purification. A small portion was removed and purified by reverse phase HPLC (85 to 100% CH3CN in H2O, both with 0.1% v/v TFA) for characterization: LCMS C, tr=3.12 min, m/z 506.2 [M+H]+; 1H NMR (500 MHz, CDCl3) δ 8.19 (d, J=1.5 Hz, 1H), 7.79 (dd, J=8.0, 2.0 Hz, 1H), 7.63 (d, J=1.5 Hz, 1H), 7.33-7.25 (m, 3H), 7.11 (s, 1H), 4.02 (s, 3H), 3.89 (s, 3H), 3.83 (dddd, J=9.0, 9.0, 6.0, 6.0 Hz, 1H), 3.21 (dd, J=13.5, 9.0 Hz, 1H), 3.06 (dd, J=13.5, 6.0 Hz, 1H), 1.91-1.83 (m, 2H), 1.63-1.56 (m, 1H), 1.39-1.26 (m, 5H), 0.86 (t, J=6.5 Hz, 3H).

Provenance & Evidence