[Synthesis]
General Steps:
Scheme I (c) Synthesis of Intermediate-9
Reagents and conditions:
i) Methanol, concentrated sulfuric acid, reflux, 3 hours;
ii) Methyl iodide, potassium carbonate, N,N-dimethylformamide, room temperature, 3 hrs;
iii) m-chloroperbenzoic acid, dichloromethane, room temperature, 12 hours;
iv) sodium hydroxide, methanol, water, room temperature, 12 hours.
Step iv: Synthesis of 2-(4-(methylsulfonyl)phenyl)acetic acid
The method of step-v of Scheme 1 (a) was used to obtain the title compound [0.56 g, 51% yield].
NMR (300 MHz, DMSO-d6): δ 12.58 (s, 1H), 7.88-7.85 (m, 2H), 7.54-7.52 (m, 2H), 3.73 (s, 2H), 3.20 (s, 3H).
Step v: Synthesis of 2-(4-(ethylsulfonyl)phenyl)acetic acid
To a 50mL round bottom flask was added ethyl 2-(4-(ethylsulfonyl)phenyl)acetate (2.5g, 0.0098mol) and ethanol (18mL). To the same flask was added aqueous sodium hydroxide (1.42 g, 0.0355 mol, dissolved in 18 mL of water) and then stirred at room temperature for 12 hours. The volatiles were evaporated under reduced pressure to give a residue. The residue was acidified with dilute hydrochloric acid to pH 5.0. The organic layer was extracted with ethyl acetate, separated, washed with brine, dried with anhydrous sodium sulfate, and evaporated under reduced pressure to give the title compound [2.4 g, 91% yield].
NMR (400 MHz, DMSO-d6): δ 12.5 (brs, 1H), 7.84 (d, 2H), 7.56 (d, 2H), 3.74 (s, 2H), 3.13 (q, 2H), 1.20 (t, 3H). |