Reaction Steps
To a stirred solution of ethyl (3-phenyl-1-{1-[4-(trifluoromethyl)phenyl]butyl}-4,5,6,7-tetrahydro-1H-indol-7-yl)acetate (107 mg, 2.2 mmol) in dioxane (5 ml) and water (0.5 ml) was added lithium hydroxide (900 mg, 22.0 mmol) and the reaction heated to reflux for 16 h. After cooling, the reaction was diluted with ethyl acetate and acidified with 2N HCl. The aqueous layer was extracted three times with ethyl acetate, and the combined organic layers dried over sodium sulfate and concentrated in vacuo. The product was purified by mass directed HPLC to give (3-phenyl-1-{1-[4-(trifluoromethyl)phenyl]butyl}-4,5,6,7-tetrahydro-1H-indol-7-yl)acetic acid (55.1 mg, 55%), a colourless foam as a 1:1 mixture of diastereomers A and B; 1H NMR δ (ppm) (CDCl3): 7.59 (2 H, d, J=8.2 Hz, A/B), 7.53 (2 H, d, J=8.1 Hz, A/B), 7.47 (2 H, d, J=8.1 Hz, A/B), 7.35 (4 H, t, J=7.3 Hz A+B), 7.21-7.13 (4 H, m, A+B), 7.06 (1 H, s, A), 6.95 (1 H, s, B), 5.19-5.11 (2 H, m, A+B), 3.39 (1 H, d, J=9.0 Hz, B), 3.06 (1 H, s, A), 2.79-2.65 (5 H, m, A+B), 2.37-2.19 (2 H, m, A+B), 2.14-2.08 (4 H, m, A+B), 2.00 (1 H, s, A/B), 1.90-1.78 (6 H, t, J=13.5 Hz, A+B), 1.74-1.70 (4 H, m, A+B), 1.42 (1 H, t, J=6.1 Hz, A/B), 1.38-1.30 (1 H, m A/B), 1.03 (3 H, t, J=7.3 Hz, A/B), 0.95 (3 H, t, J=7.3 Hz, A/B); m/z (ES−) 454 (M−H+).
