Under argon protection, 4-amino-3,5-dimethylphenol (50 mg, 0.36 mmol) and sodium 2-methylpropan-2-ol (52 mg, 0.55 mmol) were dissolved in anhydrous DMF (1 mL). Iodomethane (0.021 mL, 0.33 mmol) was then added and the reaction mixture was stirred overnight at room temperature. After the reaction was completed, dichloromethane (20 mL) was added to dilute the reaction and washed sequentially with aqueous sodium hydroxide (2 × 15 mL) and saturated saline (2 × 15 mL). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate=2/1) to afford 4-methoxy-2,6-dimethylaniline (24 mg, 43% yield). Mass spectrum (ESI+) m/z: 152.1 [M+H]+.
Methyl 7-[3-(N-(4-methoxy-2,6-dimethylphenyl)aminosulfonyl)phenyl]heptanoate (12 mg, 17% yield) was synthesized by following the procedure described in Method A using 4-methoxy-2,6-dimethylaniline (24 mg, 0.16 mmol) as starting material. Mass spectrum (ESI+) m/z: 456.2 [M+Na]+.
The above ester derivative (12 mg, 0.028 mmol) was hydrolyzed according to the hydrolysis conditions described in Method A to give compound 8 as an orange oil (11 mg, 95% yield).1H NMR (300 MHz, chloroform-d) δ ppm: 1.22-1.36 (m, 4H), 1.49-1.66 (m, 4H), 1.97 (s, 6H) , 2.30 (t, J=6.76 Hz, 2H), 2.61 (t, J=7.58 Hz, 2H), 3.75 (s, 3H), 6.53 (s, 1H), 7.31-7.39 (m, 3H), 7.46-7.57 (m, 3H). Mass spectrum (ESI+) m/z: 442.2 [M+Na]+.
