N,N,N',N'-Tetramethylethylenediamine → HCID 68504850, compound

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Reaction Steps

A solution of 3-fluoro-2-methylbenzoic acid (5.00 g, 32 mmol, 1 equiv) and N,N,N′,N′-tetramethylethylenediamine (TMEDA) (9.7 mL, 64 mmol, 2 equiv) in THF (100 mL) was cooled to −78° C. under an atmosphere of argon. s-BuLi (1.3 M in hexanes, 52 mL, 26 mmol, 2.1 equiv) was added dropwise and the solution was allowed to stir for 1 hr. A solution of 2-bromo-5-methoxybenzylbromide (22 g, 80 mmol, 2.5 equiv) in THF (10 mL) was added dropwise. The solution was allowed stir for 1 hr at −78° C. hr and then quenched by the addition of H2O and 1N HCl. The mixture was extracted with ethyl acetate. The combined organic phases were washed with brine, dried over MgSO4, filtered, and concentrated. After column chromatography (SiO2) followed by trituration from MeOH/DCM, 2-[2-(2-bromo-5-methoxy-phenyl)-ethyl]-3-fluoro-benzoic acid (3.3 g, 9.4 mmol, 80%) was obtained as a white powder. 1H NMR (300 MHz, CDCl3) δ 7.66 (d, J=7.8 Hz, 1H), 7.12-7.33 (m, 4H), 6.78 (d, J=9.0 Hz, 1H), 3.76 (s, 3H), 3.24 (t, J=7.5 Hz, 2H), 2.83 (t, J=7.5 Hz, 2H). LCMS: ES− 351 (M−1), 353 (M+1), 355 (M+3).

Provenance & Evidence