4-ETHYNYLBENZONITRILE97

To a solution of compound 38 (1.1 g, 5.3 mmol) in MeOH/THF (16 mL, 1:1) was added KTo a flask were added 32 (598.0 mg, 3.0 mmol), K4-[(trimethylsilyl)ethynyl]benzonitrile (1 mmol), inorganic base potassium tert-butoxide (sodium) or potassium hydroxide (sodium) or potassium trimethylsilylate (sodium) (0.05 mmol ), 2mL of DMA or DMSO solvent was added in turn to a 10mL sealed tube, heated and stirred in a 60°C oil bath for 12 hours, and the progress of the reaction was followed according to TLC. The reaction was completed and an equivalent of mesitylene or n-undecane was added to the crude product. As an internal standard, the exact yield of the product was determined by GC and GC-MS. According to GC and GC-MS, when DMSO is used as a reaction solvent, inorganic base potassium tert-butoxide (sodium) or potassium hydroxide (sodium) or potassium trimethylsilylate (sodium) is used as a catalyst, and the yields of the products are as follows: 49percent, 50percent, 54percent, 55percent, 82percent, 76percent. When DMA was used as the reaction solvent, the inorganic potassium tert-butoxide (sodium) or potassium hydroxide (sodium) or potassium trimethylsilylate (sodium) was used as the catalyst. The yield of the product was: 44percent, 47percent, respectively. 50percent, 49percent, 71percent, 63percent.Step 4:; [0873] TMS protected alkyne 71 (1.35 g, 1.01 mmol) was diluted with 10 mL of THF and treated with IM tetrabutylammonium fluoride in THF (1.1 mL, 1.1 mmol). After 30 min HPLC showed complete consumption of the starting material and a more polar peak. The reaction was diluted with 90 mL of water and 10 mL of 1 M aqueous HCl. The resulting solid was filtered and washed with water affording 72 as a brown solid (0.6237 g, 49percent). 1H NMR (DMSO-J6, 400 MHz): δ 7.81 (d, 2H), δ 7.62 (d, 2H), δ 4.53 (s, IH).General 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.The title compound was prepared following the procedure described in step-3 of Intermediate-1 by using 4-iodobenzonitrile (6.0 g, 26 mmol), trimethylsilyl acetylene (5.13 g, 52 mmol), CuT (10mg, 0.0005 mmol), PdC12(PPh3)2 (367 mg, 0.0005 mmol), TEA (5-lOmL) in DMSO(25 mL) at RT for 16 h to afford crude silyl compound. K2C03 (5.43 g, 39 mmol) was addedto the crude compound in THF/MeOH (1:1 ratio, 20+20 mL) and stirred further at RT for 1-2h. Then the reaction mixture was quenched with water, extracted with DCM, washed withwater, brine, dried over Na2504 and concentrated to afford 1.80 g of title product. ‘H NMR (300 MHz, CDC13): 7.56-7.63 (m, 4H), 3.30 (s, 1H).4-ethynylphenylacetylene 63 mg (0.50 mmol), silver nitrite 154 mg (1 mmol), trichloroisocyanuric acid 232.4 mg (1 mmol)Add 10 mL of pressure-resistant sealed container in turn, and then add 5 mL of acetonitrile.The mixture was stirred at room temperature, and the reaction was checked by TLC. The reaction was completed in 8 hours.The reaction solution was diluted with 10 mL of dichloromethane, and filtered to give a clear liquid.Separation by column chromatography (with petroleum ether / ethyl acetate volume ratio of 100:1 as eluent)The eluate containing the desired product were collected and the solvent was evaporated to give a white solid 4-ethynyl-benzonitrile 42.5mg (67percent yield).

Molecular Weight:127.14
XLogP3:1.9
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:1
Exact Mass:127.042199164
Monoisotopic Mass:127.042199164
Topological Polar Surface Area:23.8
Heavy Atom Count:10
Complexity:191
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes