Ammonia → (2E)-3-{4-[Cycloheptylidene(4-hydroxyphenyl)methyl]phenyl}-2-propenamide

Participants

Reaction Steps

To a stirred suspension of (2E)-3-{4-[cycloheptylidene(4-hydroxyphenyl)methyl]phenyl}-2-propenoic acid (11) (0.23 g, 0.66 mmol) in toluene (6 mL) was slowly added oxalyl chloride (0.12 mL, 0.175 g, 1.38 mmol, 2.1 eq) followed by DMF (2-3 drops) at room temperature under a nitrogen atmosphere. The reaction mixture was stirred for 0.25 h. Dichloromethane (6 mL) was added to the reaction mixture (to aid the dissolution of solids) and the reaction mixture was stirred at room temperature for 2 h. Oxalyl chloride (0.12 mL, 0.175 g, 1.38 mmol, 2.1 eq) and DMF (2 drops) were added to the reaction mixture and stirring was continued for 3 h. The reaction mixture was concentrated in vacuo. Toluene was added to the crude acid chloride and the solvent was removed in vacuo. To the crude acid chloride were added ammonia (0.5 M in 1,4-dioxane) (6 mL, 3 mmol, 4.5 eq) followed by CH2Cl2 (5 mL). The reaction mixture was stirred overnight at room temperature under a nitrogen atmosphere. The reaction mixture was transferred to a separatory funnel with the aid of CH2Cl2 and the solution was washed with water. The layers were separated and the organic phase was dried over MgSO4, filtered, and the filtrate was concentrated to give the crude amide as a gold-yellow oil. The crude product was purified by flash chromatography on silica gel with CH2Cl2:MeOH (100:0 to 95:5) to give a solid which was dried at 70° C. under vacuum to give 0.058 g (25%) of compound 13 as a tan solid. 1H NMR (400 MHz, DMSO-d6): δ 1.51 (m, 8H), 2.22 (m, 4H), 6.53 (d, J=15.9 Hz, 1H), 6.66 (d, J=8.5 Hz, 2H), 6.91 (d, J=8.3 Hz, 2H), 7.06 (br s, 1H), 7.12 (d, J=8.1 Hz, 2H), 7.35 (d, J=15.9 Hz, 1H), 7.45 (d, J=8.1 Hz, 2H), 7.50 (br s, 1H), 9.29 (s, 1H). HRMS (ESI) Calcd for C23H26NO2: 348.1964 (M+H)+. Found: 348.1951.

Provenance & Evidence