Hydrochloric Acid → 2-(3-Trifluoromethyl-5-fluoro-phenylamino)-non-8-enoic acid methyl ester

Beteiligte Stoffe

Reaktionsschritte

Reaction performed in parallel in 8×50 mL reaction flasks. Copper (II) acetate (270 mg, 1.48 mmol., 1.1 eq.) and 4 Å molecular sieves (700 mg) were charged in 50 mL round bottom flask. Dichloromethane (10 mL, previously saturated with air) was added a single portion. 2-amino-non-8-enoic acid methyl ester (250 mg, 1.35 mmol., 1.0 eq.) was added and the reaction mixture was stirred for a further 5 min by when the initial light blue solution had turned dark blue. 3-fluoro-5-trifluoromethylbenzene boronic acid (560 mg, 2.70 mmol., 2 eq.) was added followed by triethylamine (218 mg, 2.70 mmol., 2 eq.). The reaction mixture was stirred over night under an air atmosphere. The 8 reaction mixtures were combined together and 1M hydrochloric acid (150 mL) was added. The mixture was stirred for a further 5 min until the aqueous layer turned pale blue and the organic layer turned pale yellow. The organic layer was collected, dried over sodium sulfate and the solvent removed under vacuum. The residue was purified by flash column chromatography, using a dichloromethane:heptanes gradient (from neat heptane to 50% dichloromethane in heptanes). After combining the relevant fractions and solvent removal, 970 mg (26%) of the title compound was isolated as a yellow oil. 1H NMR (500 MHz, CDCl3) δ ppm 6.66 (d, J=8.54 Hz, 1 H), 6.61 (s, 1 H), 6.42 (d, J=10.83 Hz, 1 H), 5.72-5.87 (m, J=6.71, 6.71, 10.26, 17.05 Hz, 1 H), 5.00 (dd, J=1.83, 17.09 Hz, 1 H), 4.95 (dt, J=0.95, 10.15 Hz, 1 H), 4.48 (d, J=8.54 Hz, 1 H), 4.05 (dt, J=6.45, 8.32 Hz, 1 H), 3.76 (s, 3H), 2.05 (q, J=6.92 Hz, 2 H), 1.82-1.93 (m, 1 H), 1.71-1.82 (m, 1 H), 1.30-1.45 (m, 6 H). LC-MS: purity 94% (UV), tR 2.63 min, m/z [M+H]+ 348.00.

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