Ethyl 4-Ethynylbenzoate

General procedure: Some of the requisite aryl substituted terminal acetylenes (5) used as substrate in the preparation of the 1, 2, 3-triazole library of betulinic acid were prepared employing “Sonogashira reaction”[1] followed by base induced desilylation (Scheme 1), while rest of the acetylenes (5a, 5b, 5c and 5g) were purchased from commercial sources. Thus, iodide 6 (500 mg) was allowed to react with trimethyl silyl acetylene (1.5 eqv.) at room temperature in the presence of Pd(PPh3)2Cl2 (2 molpercent ), CuI (4 molpercent) and triethylamine (0.5 mL) in dry DMF under argon atmosphere to yield the intermediate product 7, which was desilylated by treating with a solution of K2CO3 (1 eqv.) dissolved in dry methanol (4.0 mL) to yield the terminal acetylene 5.S3: KSynthesis of compound 15 is as follows: A mixture of compound 14 (3.7 g, 15 mmol) and K2CO3 (4.14 g, 30 mmol) in ethanol (500 mL) was degassed with nitrogen for 30 min. The mixture solution was stirred at room temperature for 4 h. After removing the solvent, the residue was treated with water and CH2Cl2. The aqueous phase was extracted with CH2Cl2 twice. The combined organic layer was dried over anhydrous MgSO4. The solvents were removed under reduced pressure to obtain compound 14 as red-yellow oil (2.35 g, 90percent). No further purification was necessary. 1H NMR (500 MHz, CDCl3): ' = 8.00 (d, J =8.5 Hz, 2H), 7.55 (d, J =8.5 Hz, 2H), 4.38 (m, 2H), 3.22 (s, IH), 1.39 (t, J =8.0 Hz, 3H). 13C NMR (125 MHz, CDCl3) ' 166.3, 132.5 131.0, 130.0, 127.1, 83.3, 80.6, 61.6, 14.8.1.33 g (14 mmol) of trimethylsilylacetylene was added to a deoxygenated solution of 2.56 g (9.1 mmol) of compound 7, 102 mg (0.15 mmol) of Pd(PPh3)2C12, and 42 mg (0.22 mmol) of Cul in 30 mL of Et3N. The reaction solution was stirred at room temperature under argon overnight. The solvent was removed, and the solid was purified by flash chromatography on silica gel with hexane to yield a compound 8 (1.81 g, 81 ). A solution of 0.81 g (3.29 mmol) of compound 8 in 20 mL of methanol was deoxygenated for 30 min and 1.0 M tetrabutylammonium fluoride solution in THF (9.95 mmol) was added to the flask under argon and the mixture was stirred at room temperature for 6h. The solvent was removed and re-dissolved in methylene chloride and extracted with water twice. The combined organic solution was dried over MgS04 and the solvent was removed at reduced pressure to yield a compound 9 (0.38g, 66 ).1.33 g (14 rnmol) of trimethyJsiiylacetylene was added to a deoxygenated solution of 2.56 g (9.1 mmol) of compound 7, 102 mg (0.15 mmol) of Pd(PPhGeneral procedure: In a glovebox were combined aryl bromide, Pd(PPh3)2Cl2 (5 molpercent), triphenylphosphine (10 molpercent), THF (50 mL), and triethylamine (10 mL). After stirring 3 min, CuI (5 molpercent) was added and the solution was stirred another 1 min. TMS-acetylene (1.5 eq.) was then added and the reaction vessel was sealed and heated to 60 °C for 18 h. The reaction mixture was cooled, concentrated, and the residue was purified by silica gel chromatography. The obtained intermediate was then dissolved in THF (50 mL), methanol (25 mL), and a 20 percent KOH solution (aq, 15 mL) in 250 mL round bottom flask and stirred overnight at room temperature. The solution was diluted with ethyl ether (150 mL) and extracted twice with brine (50 mL). The organic layer was collected and concentrated to give a residue that was purified by silica gel chromatography.