Ammonia → (2E)-3-{4-[(4-Hydroxyphenyl)(3,3,5,5-tetramethylcyclohexylidene)methyl]phenyl}-2-propenamide

Participants

Reaction Steps

To a stirred suspension of (2E)-3-{4-[(4-hydroxyphenyl)(3,3,5,5-tetramethylcyclohexylidene)methyl]phenyl}-2-propenoic acid (16) (0.18 g, 0.46 mmol) in CH2Cl2 (6 mL) at room temperature was added oxalyl chloride (0.15 mL, 0.218 g, 1.72 mmol, 3.7 eq) followed by several drops of DMF (Note: vigorous bubbling occurred upon addition of DMF). The reaction mixture was stirred under a nitrogen atmosphere for 1 h and concentrated in vacuo. Toluene was added to the crude acid chloride and the solvent was removed in vacuo. To the crude acid chloride was added ammonia (0.5 M in 1,4-dioxane) (6 mL) and the turbid reaction mixture stirred at room temperature under a nitrogen atmosphere for 3 h. Ammonia (0.5 M in 1,4-dioxane) (2 mL) was added to the reaction mixture and stirring was continued overnight at room temperature under a nitrogen atmosphere. The reaction mixture was concentrated in vacuo. Ammonia (0.5 M in 1,4-dioxane) (8 mL) and CH2Cl2 (8 mL) were added to the residue. The flask was equipped with a rubber septum and the reaction mixture was stirred at room temperature for 2 d. The reaction mixture was transferred to a separatory funnel and partitioned between CH2Cl2 and H2O. The layers were separated and the aqueous phase was extracted with CH2Cl2. The organic extracts were combined, washed with brine, dried (MgSO4) filtered, and the filtrate was concentrated to give the crude product as an amorphous solid. The crude product was purified by flash chromatography on silica gel with CH2Cl2:MeOH (100:0 to 19:1) as eluant to provide the product which was dried to give 0.026 g (15%) of compound 17 as a pale yellow solid. 1H NMR (400 MHz, DMSO-d6): δ 0.87 (s, 6H), 0.88 (s, 6H), 1.25 (s, 2H), 1.89 (s, 2H), 1.92 (s, 2H), 6.53 (d, J=15.8 Hz, 1H), 6.66 (d, J=8.5 Hz, 2H), 6.93 (d, J=8.5 Hz, 2H), 7.06 (br s, 1), 7.14 (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), 9.30 (s, 1). HRMS (ESI) Calcd for C26H32 NO2: 390.2433 (M+H)+. Found: 390.2427.

Provenance & Evidence