Lithium Hydroxide → 2-(5-{3-[5-(4,5,6,7-Tetrahydro-benzothiazol-2-yl)-pyridin-2-yloxy]-propoxy}-indol-1-yl)-propionic acid

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Reaction Steps

To a solution of 3-[5-(4,5,6,7-tetrahydro-benzothiazol-2-yl)-pyridin-2-yloxy]-propan-1-ol (Example 78, 0.098 g, 0.34 mmol) and 2-(5-hydroxy-indol-1-yl)-propionic acid methyl ester (Example 7, 0.067 g, 0.31 mmol) in CH2Cl2 (10 mL) were added triphenylphosphine (0.161 g, 0.61 mmol) and 1,1′-(azodicarbonyl)-dipiperidine (0.155 g, 0.61 mmol). The yellow reaction mixture was stirred at rt for 18 h, then diluted with 20 mL hexanes, and filtered through a short pad of silica gel. The filtrate was concentrated under reduced pressure, and the residue (0.065 g) dissolved in 5 mL of a mixture of methanol/THF/water (2:2:1). LiOH (9.1 mg, 0.37 mmol) was added. The mixture was stirred at rt for 18 h and concentrated under reduced pressure. The residue was taken up in water and washed with ether. The aqueous layer was acidified to pH 3.5 and extracted with ethyl acetate. The combined organic layers were dried over Na2SO4, filtered, and concentrated to give the title compound (7 mg, 4%). 1H NMR (400 MHz, acetone-d6) δ 8.20 (dd, 1H), 7.90 (dd, 1H), 7.35 (s, 1H), 7.29 (dd, 1H), 7.11 (s, 1H), 6.85 (dd, 1H), 6.50 (dd, 1H), 6.39 (s, 1H), 5.25-5.35 (m, 1H), 4.31 (t, 2H), 4.31 (t, 2H), 4.08 (t, 2H), 2.95-3.05 (br s, 1H), 2.70-2.78 (m, 4H), 2.30-2.35 (m, 2H), 1.70-1.94 (m, 4H). LC/MS m/z 478.2 (M+H)+, RT 2.90 min.

Provenance & Evidence