1-Hydroxybenzotriazole → 4-[(4-butylphenyl)ethynyl]-N-[(2,2-dimethyl-4-oxo-4H-1,3-benzodioxin-6-yl)methyl]-N-hexylbenzamide

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Reaction Steps

A solution of 4-(4-butylphenylethynyl)benzoic acid (330 mg, 1.19 mmol), EDC.HCl (231 mg, 1.21 mmol), HOBT (163 mg, 1.21 mmol) and DIEA (256 μl, 1.51 mmol) in DCM (15 mL) was stirred 10 min at rt. Then a solution of 6-[(hexylamino)methyl]-2,2-dimethyl-4H-1,3-benzodioxin-4-one (293 mg, 1.01 mmol) in DCM (5 mL) was added and the resulting mixture was stirred 3 hrs at rt. The reaction mixture was diluted with DCM and washed with a saturated aqueous solution of NaHCO3, an aqueous solution of HCl (1N) and brine. Organic layer was dried over MgSO4 and the solvent was removed under reduced pressure. Purification by flash chromatography on silica gel (EtOAc/c-Hex (20/80)) gave 420 mg (73%) of the title compound. HPLC, Rt: 6.18 min (purity: 92.3%). A second purification by preparative HPLC with a X-Terra column allowed the isolation of the title compound (300 mg, 54% yield) as a white powder. HPLC, Rt: 6.15 min (purity: 99.1%). LC/MS, M+(ESI): 552.7. 1H NMR (CDCl3) δ: 0.82 (m, 3H), 0.91 (t, J=7.3 Hz, 3H), 1.09-1.41 (m, 8H), 1.53 (m, 4H), 1.72 (s, 6H), 2.60 (t, J=7.6 Hz, 2H), 3.16-3.45 (m, 2H), 4.50-4.70 (m, 2H), 6.96 (d, J=8.5 Hz, 1H), 7.15 (d, J=8.1 Hz, 2H), 7.37 (d, J=8.3 Hz, 2H), 7.42 (d, J=7.9 Hz, 2H), 7.52-7.84 (m, 4H).

Provenance & Evidence