Diisopropylethylamine → 2,4-dibromo-N-(3-fluoro-4-methylbenzyl)butanamide

Participants

Reaction Steps

To a stirring 0° C. solution of 3-fluoro-4-methylbenzyl amine (2.0 g, 14 mmol) and N-ethyl-N-isopropylpropan-2-amine (3.5 mL, 20 mmol) in dichloromethane (30 mL) was added dropwise a solution of 2,4-dibromobutanoyl chloride (3.98 g, 15 mmol) in dichloromethane (5 mL). After completion of the addition, the reaction was stirred in the ice bath until all of the ice had melted, then it was partitioned between ethyl acetate and water. The layers were separated, the organic layer was washed with brine, and it was then dried over magnesium sulfate. The drying agent was filtered off, the solvent was evaporated, and the residue was dissolved in ethyl acetate and subjected to silica gel chromatography in 10→25→100% ethyl acetate/hexane, collecting the main component to yield 4.5 g (85%) 2,4-dibromo-N-(3-fluoro-4-methylbenzyl)butanamide. LCMS (method CZ-1): RT 1.21 min, m/z 367.9 (MH+); 1H NMR (500 MHz, chloroform-d) δ 7.17 (t, J=7.7 Hz, 1H), 7.01-6.91 (m, 2H), 6.70 (br. s., 1H), 4.59 (dd, J=9.0, 4.9 Hz, 1H), 4.51-4.37 (m, 2H), 3.64-3.51 (m, 2H), 2.71 (dddd, J=15.0, 8.5, 6.1, 4.9 Hz, 1H), 2.51 (ddt, J=15.0, 9.2, 5.5 Hz, 1H), 2.27 (d, J=1.4 Hz, 3H).

Provenance & Evidence