Lithium Hydroxide → 1-((3-Fluoro-4-(5-(phenylmethyl)-1H-indol-2-yl)phenyl)methyl)-3-azetidinecarboxylic acid

Participants

Reaction Steps

To a solution of methyl 1-(4-(5-benzyl-1H-indol-2-yl)-3-fluorobenzyl)azetidine-3-carboxylate (0.090 g, 0.21 mmol) in THF (1.0 mL) and water (1.0 mL) was added lithium hydroxide (0.025 g, 1.1 mmol). The solution was stirred at rt for 1 h, or until starting material was no longer observed by LCMS. The solvent was removed under reduced pressure, and 0.5M phosphate buffer (3.0 mL, pH 6.0) was added (pH was ca. 9-10). The mixture was acidified with 1N HCl to pH 6.0 and sonicated for 5 min. The aqueous solution was extracted with EtOAc (3×15 mL), and the separated organic extracts were dried over MgSO4, filtered and concentrated to afford a brown oil. The oil was dissolved in AcOH (3.0 mL), and the excess AcOH was removed under reduced pressure. Ether (15 mL) was added, and the resulting precipitate was collected by filtration. The brown solids were washed with water (10 mL) and chloroform (15 mL) to afford title compound as a yellow solid [hS1P1 EC50=1336 nM]. MS (ESI) m/z: Calculated: 414.1; Observed: 415.1 (M++1).

Provenance & Evidence