Hydrochloric Acid → 2-[4-(2-Heptylamino-ethyl)-phenylamino]-2-methyl-propionic acid

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Reaction Steps

1H NMR (400 MHz, CDCl3) δ6.98 (d, 2H), 6.59 (d, 2H), 5.38 (s, 1H), 4.03 (s, 1H), 3.47 (m, 2H), 2.70 (t, 2H), 2.11 (t, 2H), 1.65−1.40 (m, 3H), 1.53 (s, 6H), 1.39 (s, 9H), 1.29 (m, 5H), 0.89 (t, 3H). Borane-tetrahydrofuran complex (1.0M in THF; 6.96 mL, 6.96 mmol) was added to a solution of 2-[4-(2-heptanoylamino-ethyl)-phenylamino]-2-methyl-propionic acid tert-butyl ester (1.36 g, 3.48 mmol) and tetrahydrofuran (25 mL) and the resulting mixture stirred at ambient temperature for 18 h. Additional borane-tetrahydrofuran complex (3.5 mL, 3.5 mmol) was added and the resulting mixture stirred 24 h at ambient temperature before acidifying with 1N aqueous hydrochloric acid. The resulting mixture was then refluxed for 2 h, cooled to ambient temperature and the tetrahydrofuran removed under reduced pressure. The resulting residue was neutralized with saturated aqueous sodium bicarbonate, concentrated under reduced pressure, azeotroped with ethyl acetate and purified by flash column chromatography (10% methanol/1% concentrated ammonium hydroxide/chloroform→15% methanol/1% concentrated ammonium hydroxide/chloroform) to provide 417 mg (38%) of 2-[4-(2-heptylamino-ethyl)-phenylamino]-2-methyl-propionic acid as a white solid.

Provenance & Evidence