Hydrochloric Acid → 5-(6-(4-Fluorobenzylcarbamoyl)-2-phenylquinolin-3-yl)pentanoic acid

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Reaction Steps

A solution of 5-(6-bromo-2-phenylquinolin-3-yl)pentanoic acid (1A, 100 mg, 0.260 mmol) in THF (4.00 mL, 49.3 mmol) in a flame dried vial under an atmosphere of nitrogen gas was treated with lithium hexamethyldisilazide (1M/THF, 780 uL). The reaction mixture stirred at RT for 10 min before it was cooled to −78° C. in an acetone/dry ice bath. A solution of nBuLi (2.5M/hexane, 229.0 uL) was slowly added and the reaction progressed for 5 minutes at −78° C. before addition of 4-fluorobenzyl isocyanate (398 uL, 3.12 mmol). The reaction was stirred at −78° C. for 20 minutes, acidified with 10% HCl to pH 1, and diluted with DCM. The biphasic solution was separated and the aqueous layer was extracted with DCM (3×). The combined organic phase was dried over anhydrous sodium sulfate, concentrated and chromatographed (5-100% EtOAc/hexanes) to provide 2 (28 mg; Yield=24%, LCMS (M+H)=439).

Provenance & Evidence