Hexanal → Methyl 5-[{4-[(4-ethylphenyl)ethynyl]benzyl}(hexyl)amino]-2-fluorobenzoate

Participants

Reaction Conditions

Reaction Steps

To a solution of 4-[(4-ethylphenyl)ethynyl]benzaldehyde (530 mg; 2.26 mmol, intermediate which may be prepared according to methods disclosed in EP03103780.7) in toluene (35 mL) were added methyl 5-amino-2-fluorobenzoate (382 mg; 2.26 mmol) and AcOH (194 μL) and the reaction mixture was refluxed with azeotropic removal of water until complete consumption of, the aldehyde (determined by 1H NMR of aliquots). Toluene was concentrated under reduced pressure and the residue dissolved in DCE (25 mL). Hexanal (Aldrich, 818 μl; 6.79 mmol), acetic acid (194 μL) and sodium triacetoxyborohydride (1,4 g, 6.79 mmol) were added to the solution, which was then heated at 60° C. for 3 hrs. The reaction mixture was poured into a saturated solution of NaHCO3 and extracted twice with DCM. Combined organic layers were washed with brine, dried over magnesium sulfate, filtrated and concentrated to give 1.4 g of a brown solid. Purification by flash chromatography using silica gel (EtOAc/c-Hex, gradient from 97:3 to 95:5) yielded to 330 mg (30%) of the title compound as a white solid. HPLC, Rt: 6.27 min (purity: 61%), LC/MS, M+(ESI): 472.2, 1H NMR (CDCl3) δ: 7.43 (t, J=7.7 Hz, 4H), 7.17 (m, 5H), 6.90 (t, J=10.7 Hz, 1H), 6.73 (m, 1H), 4.49 (s, 2H), 3.88 (s, 3H), 3.35 (t, J=7.8 Hz, 2H), 2.63 (qd, J=7.5 Hz, 2H), 1.61 (m, 2H), 1.28 (m, 6H), 1.22 (t, J=7.6 Hz, 3H), 0.85 (t, J=5.1 Hz, 3H).

Provenance & Evidence