Reaction Steps
3-n-Propyl-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalene (prepared from Friedel-Crafts alkylation/cyclization of n-propylbenzene with 2,5-dichloro-2,5-dimethylhexane) was combined with monomethylterephthalate acid chloride in dichloromethane and treated portionwise at ambient temperature with aluminum chloride until the spontaneous reflux had subsided and the solution become dark red/brown in color. After stirring at room temperature for 10-15 min, the reaction was poured into ice water and the layers were separated. The aqueous layer was extracted with EtOAc. The combined organic extracts were washed with water and brine, dried (MgSO4), filtered, and concentrated to give a yellow oil. The crude product was crystallized (CH2Cl2/hexanes) to give 4-[(3-n-propyl-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)carbonyl]benzoic acid methyl ester as white crystals (95%): TLC (20% ethyl acetate: 80% hexanes) Rf 0.7; mp 112-114° C.; 1H-NMR (400 MHz, CDCl3) δ8.19 (½ABq, J=8.0 Hz, 2H, ArH); 7.89 (½ABq, J=8.0 Hz, 2H, ArH), 7.22 (s, 1H, ArH), 7.20 (s, 1H, ArH), 3.95 (s, 3H, OCH3), 2.64 (t, J=8.0 Hz, 2H, CH2), 1.69 (s, 4H, 2CH2), 1.55 (m, 2H, CH2), 1.31 (s, 6H, 2CH3), 1.20 (s, 6H, 2CH3), 0.89 (t, J=7.5 Hz, 3H, CH3), Anal. (C23H32O3) C, H. The ester was hydrolyzed in excess KOH/MeOH at ambient temperature for 24 h. The methanol was removed in vacuo. The residue was taken-up in water and the aqueous layer was adjusted to pH=4-5 with 1 M aqueous HCl. The aqueous solution was extracted 3 times with EtOAc; the organic layers were combined, and washed with water (2×) and brine. The organic solution was dried (Na2SO4), filtered, and concentrated to give 4-[(3-n-propyl-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)carbonyl]benzoic acid (101). Crystallization gave a white powder (93%): TLC (10% MeOH: 90% CHCl3) Rf 0.3; mp 252-254° C.; 1H-NMR (400 MHz, CDCl3) δ8.20 (½ABq, J=8.0 Hz, 2H, ArH), 7.90 (½Abq, J=8.0 Hz, 2H, ArH), 7.20 (s, 1H, ArH), 7.25 (s, 1H, ArH), 2.64 (t, J=8.0 Hz, 2H, CH2), 1.69 (s, 4H, 2CH2), 1.55 (m, 2H, CH2), 1.31 (s, 6H, 2CH3), 1.20 (s, 6H, 2CH3), 0.89 (t, J=7.5 Hz, 3H, CH3), Anal. (C25H30O3) C, H.
