Hydrochloric Acid → 2-(7-(4-Neopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic Acid

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Reaction Steps

Ethyl 2-(7-(4-chloro-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetate (200 mg, 0.443 mmol) was dissolved in THF (7.0 mL) and neopentylzinc(II) iodide (2.66 mL of a 0.5 M solution in THF) and bis(tri-t-butylphosphine)palladium(0) (0.011 g, 0.022 mmol) were added. The reaction mixture was stirred at room temperature for 16 h and then warmed to 50° C. After stirring for 24 h, neopentylzinc(II) iodide (5.0 mL of a 0.5 M solution in THF) was added and the reaction mixture was heated to 90° C. The reaction vessel was cooled to room temperature before 1.0 M LiOH (5 mL) and dioxane (5.0 mL) were added. After stirring for 24 h, the reaction was acidified with 1.0 M HCl to pH 3 and extracted three times with EtOAc. The combined extracts were dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by HPLC. The purified fractions were neutralized with sodium bicarbonate and then acidified to pH 5 with 1.0 M citric acid. The aqueous mixture was extracted with EtOAc and the organic layer was washed two times with water. The EtOAc layer was dried over sodium sulfate, filtered and concentrated under reduced pressure to provide the title compound (12.3 mg). LCMS m/z=460.6 [M+H]+; 1H NMR (400 MHz, CDCl3) δ ppm 0.96 (s, 9H), 2.08-2.19 (m, 1H), 2.61 (dd, J=17.0, 10.9 Hz, 1H), 2.73-2.90 (m, 6H), 3.54-3.63 (m, 1H), 5.09 (s, 2H), 6.85 (dd, J=8.8, 2.5 Hz, 1H), 7.0 (d, J=2.5 Hz, 1H), 7.22 (d, J=9.0 Hz, 1H), 7.36 (d, J=8.0 Hz, 1H), 7.55 (d, J=8.1 Hz, 1H), 7.74 (d, J=1.1 Hz, 1H), 8.29 (bs, 1H).

Provenance & Evidence