* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Reference：
[1] European Journal of Organic Chemistry, 2016, vol. 2016, # 18, p. 3056 - 3059
2
[ 10602-03-6 ]
[ 10602-00-3 ]
Reference：
[1] Dalton Transactions, 2009, # 44, p. 9794 - 9799
[2] Journal of Organic Chemistry, 1966, vol. 31, p. 2585 - 2593
3
[ 10602-03-6 ]
[ 10602-04-7 ]
Reference：
[1] Journal of Organic Chemistry, 1966, vol. 31, p. 2585 - 2593
4
[ 150969-54-3 ]
[ 10602-03-6 ]
Yield
Reaction Conditions
Operation in experiment
95%
With potassium carbonate In methanol at 20℃; for 2 h; Inert atmosphere
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.
94%
at 20℃; for 2 h;
S3: K2CO3 (0.426 g, 3.044 mmol) was added to a solution of S2 (0.250 g, 1.01 mmol) in MeOH (10 mL) and stirred at room temperature for 2 h. The solid material was isolated by filtration and the solvent was removed in vacuo. The residue was then dissolved in CH2Cl2 (5 mL) before being washed with H2O (3 mL x 2) and brine (3 mL). The organic phase was then dried (Na2SO4). The solvent was removed in vacuo. Column chromatography (SiO2: Hexanes / CH2Cl2 = 3: 1) afforded the product S3 as a white solid (0.180 g, 94percent). IH NMR (500 MHz, CDC13): δ = 7.97 (d, 2H, Ar-Ha, 3J = 8.7 Hz), 7.54 (d, 2H, Ar-Hb, 3J = 8.7 Hz), 3.92 (s, 3H, OCH3), 3.23 (s, I H, CDCH). 13C NMR (CDCl3, 125 MHz): δ = 166.3, 131.9, 130.0, 129.3, 126.6, 82.7, 79.9, 52.1. HiRes MS (ESI-TOF): Calcd. for [M + H]+ C10H9O2+ = 161.0597; found m/z = 161.0590. (see, e.g., Fig. 8).
90%
at 20℃; for 4 h;
Synthesis 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.
66%
With methanol; tetrabutyl ammonium fluoride In tetrahydrofuran at 20℃; for 6 h; Inert atmosphere
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 ).
66%
With tetrabutyl ammonium fluoride In tetrahydrofuran; methanol at 20℃; for 6 h; Inert atmosphere
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(PPh3)2Cl2, and 42 mg (0.22 mmol) of Cul in 30 mL of Et3N. The reaction soluiion 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 percent). 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 percent). Ή NMR (500 MHz, CfX 'l . s δ 7.80 (d, 2H), 7.54 (d, 2H), 4.38 (m, 2H), 3.24 (s, M l ). 1.39 (t, 3H).
0.87 g
With potassium hydroxide In tetrahydrofuran; methanol; water at 20℃; Inert atmosphere
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.
Reference：
[1] Chemistry - A European Journal, 2011, vol. 17, # 34, p. 9320 - 9325
[2] European Journal of Medicinal Chemistry, 2015, vol. 102, p. 93 - 105
[3] Patent: WO2009/149381, 2009, A2, . Location in patent: Page/Page column 32
[4] Journal of Polymer Science, Part A: Polymer Chemistry, 2011, vol. 49, # 1, p. 211 - 224
[5] Journal of the American Chemical Society, 2015, vol. 137, # 1, p. 413 - 419
[6] Journal of Medicinal Chemistry, 2000, vol. 43, # 20, p. 3736 - 3745
[7] Organic and Biomolecular Chemistry, 2015, vol. 13, # 33, p. 8886 - 8892
[8] Patent: WO2009/158606, 2009, A2, . Location in patent: Page/Page column 5
[9] Patent: WO2012/9472, 2012, A2, . Location in patent: Page/Page column 3; 7
[10] Patent: WO2013/20096, 2013, A2, . Location in patent: Page/Page column 47-48
[11] Journal of the American Chemical Society, 1997, vol. 119, # 27, p. 6345 - 6359
[12] Chemical and Pharmaceutical Bulletin, 1999, vol. 47, # 3, p. 398 - 404
[13] Tetrahedron Letters, 2004, vol. 45, # 8, p. 1693 - 1697
[14] Tetrahedron Letters, 2015, vol. 56, # 51, p. 7105 - 7107
[15] Advanced Synthesis and Catalysis, 2016, vol. 358, # 15, p. 2436 - 2442
[16] European Journal of Organic Chemistry, 2016, vol. 2016, # 18, p. 3056 - 3059
With potassium carbonate; In methanol; at 20℃; for 2h;Inert atmosphere;
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 mol% ), CuI (4 mol%) 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.
94%
With methanol; potassium carbonate; at 20℃; for 2h;
S3: K2CO3 (0.426 g, 3.044 mmol) was added to a solution of S2 (0.250 g, 1.01 mmol) in MeOH (10 mL) and stirred at room temperature for 2 h. The solid material was isolated by filtration and the solvent was removed in vacuo. The residue was then dissolved in CH2Cl2 (5 mL) before being washed with H2O (3 mL x 2) and brine (3 mL). The organic phase was then dried (Na2SO4). The solvent was removed in vacuo. Column chromatography (SiO2: Hexanes / CH2Cl2 = 3: 1) afforded the product S3 as a white solid (0.180 g, 94%). IH NMR (500 MHz, CDC13): delta = 7.97 (d, 2H, Ar-Ha, 3J = 8.7 Hz), 7.54 (d, 2H, Ar-Hb, 3J = 8.7 Hz), 3.92 (s, 3H, OCH3), 3.23 (s, I H, CDCH). 13C NMR (CDCl3, 125 MHz): delta = 166.3, 131.9, 130.0, 129.3, 126.6, 82.7, 79.9, 52.1. HiRes MS (ESI-TOF): Calcd. for [M + H]+ C10H9O2+ = 161.0597; found m/z = 161.0590. (see, e.g., Fig. 8).
90%
With ethanol; potassium carbonate; at 20℃; for 4h;
Synthesis 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, 90%). 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.
66%
With methanol; tetrabutyl ammonium fluoride; In tetrahydrofuran; at 20℃; for 6h;Inert atmosphere;
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 ).
66%
With tetrabutyl ammonium fluoride; In tetrahydrofuran; methanol; at 20℃; for 6h;Inert atmosphere;
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(PPh3)2Cl2, and 42 mg (0.22 mmol) of Cul in 30 mL of Et3N. The reaction soluiion 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 %). ? NMR (500 MHz, CfX 'l . s delta 7.80 (d, 2H), 7.54 (d, 2H), 4.38 (m, 2H), 3.24 (s, M l ). 1.39 (t, 3H).
0.87 g
With potassium hydroxide; In tetrahydrofuran; methanol; water; at 20℃;Inert atmosphere;
General procedure: In a glovebox were combined aryl bromide, Pd(PPh3)2Cl2 (5 mol%), triphenylphosphine (10 mol%), THF (50 mL), and triethylamine (10 mL). After stirring 3 min, CuI (5 mol%) 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 % 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.
With copper(l) iodide; triethylamine;bis(triphenylphosphine)palladium(II)-chloride; In water; at 60℃; for 2h;
Step 3-Preparation of 4-[1-Benzenesulfonyl-5-(3,4-dimethoxy-phenyl)-1H-pyrrolo[2,3-b]pyridin-3-ylethynyl]-benzoic acid ethyl ester 135 1-Benzenesulfonyl-5-(3,4-dimethoxy-phenyl)-3-iodo-1H-pyrrolo[2,3-b]pyridine (0.0800 g, 0.000151 mol), 4-Ethynyl-benzoic acid ethyl ester (0.0321 g, 0.000181 mol), Bis(triphenylphosphine)palladium(II) chloride (0.0048 g, 0.0000069 mol), and Copper(I) iodide (0.00024 g, 0.0000013 mol) were dissolved in Triethylamine (0.8 mL, 0.005 mol) under an atmosphere of Nitrogen. The resulting mixture was heated to 60 C. and stirred under an atmosphere of Nitrogen for 2 hours. The reaction mixture was was concentrated under reduced pressure and water (30 mL) was added to the residue. This slurry was extracted with ether. (20 mL 2*). The combined organic layers were washed with brine, dried over sodium sulfate and concentrated under reduced pressure. The crude was purified by chromatography (Silica gel, ethyl acetate/hexanes to give 85 mg of the titled product as a pale orange solid. MS(ESI) [M+H+]+=567.10
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; In N,N-dimethyl-formamide; at 50℃; for 3h;
A solution of 3,5-dichloropicolinonitrile (commercially available) (1.0 eq.), <strong>[10602-03-6]ethyl 4-ethynylbenzoate</strong> (commercially available) (1.0 eq.), trans-dichlororbis(triphenylphosphine)palladium (II) (10 mol %), copper (I) iodide (20 mol %), and triethylamine (5.0 eq.) in DMF (0.3 M) was stirred at 50 C. for 3 hours. After cooling to ambient temperature, the reaction mixture was diluted with ethyl acetate and 10% aqueous ammonium hydroxide. The two phases were separated, and the aqueous layer was extracted twice with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous MgSO4, and concentrated en vaccuo. The crude material was purified by flash chromatography on a COMBIFLASH, system (ISCO) using 0-20% ethyl acetate in hexane to give ethyl 4-((5-chloro-6-cyanopyridin-3-yl)ethynyl)benzoate as a white solid.
With triethylamine;copper(l) iodide; trans-dichlorobis(triphenylphosphine)platinum(II); In N,N-dimethyl-formamide; at 50℃; for 3h;
A solution of S.S-dichloropicolinonitrile (commercially available) (1.0 eq.), ethyl 4- ethynylbenzoate (commercially available) (1.0 eq.), trans- dichlororbis(triphenylphosphine)palladium (II) (10 mol%), copper (I) iodide (20 mol%), and triethylamine (5.0 eq.) in DMF (0.3 M) was stirred at 5O0C for 3 hours. After cooling to ambient temperature, the reaction mixture was diluted with ethyl acetate and 10% aqueous ammonium hydroxide. The two phases were separated, and the aqueous layer was extracted twice with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous MgSO4, and concentrated en vaccuo. The crude material was purified by flash chromatography on a COMBIFLASH system (ISCO) using 0-20% ethyl acetate in hexane to give ethyl 4-((5-chloro- 6-cyanopyridin-3-yl)ethynyl)benzoate as a white solid .
With copper(l) iodide; diisopropylamine;bis-triphenylphosphine-palladium(II) chloride; In N,N-dimethyl-formamide; at 90℃; for 48h;Inert atmosphere;
S6: S5 (0.100 g, 0.144 mmol) and S3 (0.0510 g, 0.317 mmol) were dissolved in a mixture of DMF (3 mL) and iPr2NH (1 mL). Under Ar protection, Pd(PPh3)2CI2 (0.010 g, 0.014 mmol) and CuI (0.003 g, 0.014 mmol) were added to the solution. The mixture was stirred under Ar at 90 0C for 48 h before the solvent was removed in vacuo. The residue was then dissolved in CH2Cl2 (5 mL) before being washed with H2O (3 mL x 2) and brine (3 mL). The organic phase was dried (Na2SO,)) and the solvent was then removed in vacuo. Column chromatography (SiO2: Et2O / CH2C12 = 2: 1 ) provided product S6 as a yellow fluorescent solid (0.101 g, 84.0%). I H NMR (500 MHz, CDC13): delta = 8.02 (d, 4H, Ar-Ha, 3J = 8.2 Hz), 7.60 (d, 4H, Ar-Hb, 3J = 8.2 Hz), 7.00 (s, 2H, Ar-HQl ), 6.68 (s, 4H, Ar-HQ2), 4.13-3.64 (m, 32H, OCH2O), 3.94 (s, 3H, OCH3). 13C NMR (CDC13, 125 MHz): delta = 166.4, 153.7, 152.9, 131.4, 129.4, 129.4, 127.9, 117.0, 115.3, 94.5, 88.7, 71.0, 70.9, 70.7, 70.6, 69.6, 69.6, 69.5, 68.0, 52.1. HiRes MS (ESl-TOF): Calcd. for [M + H]+ C48H53Oi4+ m/z = 853.3430; found m/z = 853.3433. (see, e.g., Fig. 10).
ethyl 4-(3-hydroxy-3-methylbut-1-yn-1-yl)benzoate[ No CAS ]
[ 10602-03-6 ]
Yield
Reaction Conditions
Operation in experiment
65%
With sodium hydride; In hexane; for 48h;Inert atmosphere; Reflux;
To a solution of ethyl 4-(3-hydroxy-3-methylbut-1-yn-1-yl) benzoate 34 (1.0 mmol) in hexane (12 mL mmol-1),NaH (1.8 mmol) was added. The reaction mixture wasrefluxed under nitrogen atmosphere for 48 h. The reactionwas extracted with ethyl acetate and the organic phase wasdried over MgSO4. The solvent was removed under vacuum.The product was purified by flash chromatography on silicagel using hexane as eluent. The product 35 was obtainedas a yellow oil in 65% yield. 1H NMR (300 MHz, CDCl3) delta 1.37 (t, 3H, J 6 Hz, CH3), 3.20 (s, 1H, CH), 4.35 (q, 2H,J 6 Hz, CH2), 7.52 (d, 2H, J 9 Hz, Ar-H), 7.97 (d, 2H,J 9 Hz, Ar-H); 13C NMR (75 MHz, CDCl3) delta 14.27, 61.18,79.93, 82.83, 126.59, 129.40, 130.48, 132.01, 165.91.
With 2,2'-azobis-(2,4-dimethylvaleronitrile); In neat liquid; at 60℃; for 6h;Inert atmosphere; Sealed tube;
General procedure: To a 20 mL screw capped test tube, ethynylbenzene 1a (1.0 mmol, 102 mg), 3-bromopropene 2a (5 mL), and V-65 [2,2'-azobis(2,4-dimethylvaleronitrile)] (0.2 mmol, 50 mg) were added. Then, this test tube was purged with argon and sealed. The mixture was stirred at 60 C for 6 h under argon atmosphere. The reaction mixture was concentrated under reduced pressure. The residue was purified by flash column chromatography on SiO2 using hexane to give the corresponding 1-bromo-2-phenyl-1,4-pentadiene 3aa (179 mg, 80%).
General procedure: A 50 mL of round bottom flask was added copper (I)thiophene-2-carboxylate (CuTC, 0.1 mmol, 0.1 eq in regards to alkyne), toluene(10 mL), and the alkyne (1.0 mmol, 1.0 eq). The reaction mixture was stirred atroom temperature. Subsequently, the sulfonyl azide (1.0 mmol, 1.0 eq) was addedslowly. After completion of the reaction as indicated by TLC, the reactionmixture was diluted with saturated aq.NH4Cl (10 mL) and extracted into EtOAc (2 10mL). The combined organics were dried (Na2SO4) andfiltered through celite. The eluent was concentrated in vacuo and the residue was purified by column chromatography onsilica gel (eluted with PE/EA = 8 : 1) to give the 1-Sulfonyl-1,2,3-triazoles (1a-l).
1,4-bis(3-bromopropoxy)-2,5-diiodobenzene[ No CAS ]
[ 10602-03-6 ]
4Br(1-)*C58H82N4O6(4+)[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
85%
With diisopropylamine;copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); In water; N,N-dimethyl-formamide; at 20℃; for 18h;Inert atmosphere;
A solution of 0.1 g (0.087 mmol) of compound 6 and 0.033 g (0.191 mmol) of compound 9 in 4 mL of DMF/(iPr)2NH mixture was deoxygenated for 30 min. 4 mg (3 muiotaetaomicron) of Pd(PPh3)4, and 1 mg (5 muiotaetaomicron) of Cul were added and the resulting mixture was stirred at room temperature under argon for 18 h. The reaction solution was poured into 100 mL of acetone. The precipitated solid was collected by vacuum filtration and recrystallized from water, yield 0.09 g (85 ).
85%
With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); diisopropylamine; In water; N,N-dimethyl-formamide; at 20℃; for 18h;Inert atmosphere;
A solution of 0.1 g (0.087 mmol) of compound 6 and 0.033 g (0.191 mmol) of compound 9 in 4 mL of DMF/(iPr)2NH mixture was deoxygenated for 30 mm. 4 mg (3 muetaiotaomicron?) of Pd(PPli3)4, and 1 mg (5 muetaiotaomicron?) of CuT were added and the resulting mixture was stirred at room temperature under argon for 18 h. The reaction solution w as poured into 100 mL of acetone. The precipitated solid was collected by vacuum filtration and recry taliized from water, yield 0.09 g (85 %). JH NMR (500 MHz, DMSO~d6) delta 8.04 (br, 4F1), 7.71 (br, 4H), 7.36 (br, 2H), 4.33 (br, 4H), 4.19 (br, 4FI), 3.95 - 3.74 (br, 28H), 3.51 (br, 4H), 2.07 (br, 4H), 1.68 (br, 4H), 1.31 (br, 18H), 0.89 (br, 6H). ] 3C NMR (500 MHz, DMSO- d6) delta 165.1 1 , 152.93, 131.71 , 129.72, 129.57, 126.83, 1 17.56, 1 13.30, 94.37, 88.56, 66.26, 63.38, 50.57, 50.41 , 30.59, 25.16, 21.96, 21.80, 21.27, 14.16, 13.91. ESI MS calcd m/z for [ +2Br]2+ 545.2289, found 545.2295.
With copper(I) thiophene-2-carboxylate; rhodium(II) pivalate; In chloroform; at 20 - 120℃; for 6.5h;Microwave irradiation;
General procedure: Phenylethyne 1a (20.4 mg, 0.20 mmol), TsN3 (39.4 mg, 0.20 mmol), allyl phenyl sulfide 2a (33.1 mg, 0.22 mmol), CuTC (3.8 mg, 20 mumol), Rh2(OCOt-Bu)4 (3.1 mg, 5 mumol), and chloroform (2 mL) were added to a 2-5 mL Biotage microwave vial equipped with a stir bar. The vial was sealed with a Teflon pressure cap. The reaction mixture was stirred at room temperature for 6 h, and then, heated at 120 C for 30 min under microwave irradiation. After the reaction mixture was cooled in ice-water bath, lithium aluminum hydride solution (2.5 mol/L in THF, 0.1 mL, 0.25 mmol) was added dropwise at 0 C. The resulting mixture was stirred for 30 minutes at 0 C, and quenched with 0.1 mL of methanol. The resulting mixture was diluted with 1N HCl (3 mL) and extracted with ethyl acetate (3 x 10 mL). The combined organic layers were washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by preparative thin-layer chromatography(Hexane/Ethyl acetate = 2:1) to give the amine 4aa as a white solid (62.7 mg, 0.15 mmol, 74%).
The 1,4- phenyl-diiodide in dissolved in anhydrous methylene chloride, to add a second isopropylamines, get colorless solution, in the system after the tea argon parfait under ice bath, adding three a base silicon acetylene, b (triphenylphosphine) palladium chloride, cuprous iodide. After finishing the reaction, methylene chloride is added after diluting the reaction system, sequentially adding a saturated's amine chloride solution, pure water is washed and after washing with saturated sodium chloride, collecting the organic phase, and an appropriate amount of anhydrous magnesium sulfate for drying, filtering to remove the magnesium sulfate, collecting the organic phase, and the spin vaporization under reduced pressure to remove organic solvent to obtain darkred brown oily liquid, the liquid re-dissolved in the methanol and dichloromethane (volume ratio = 1:1) in the mixed solution, adding anhydrous potassium carbonate, stirring at room temperature, filter to remove solid, reducing the spin vaporization of the remaining liquid removal of the organic solvent to the darkred brown oily liquid, by adding dichloromethane to dissolve, for successively 1mol/L washing with hydrochloric acid, saturated sodium bicarbonate washing, pure water washing and saturated salt water washing, to collect organic solution, and with appropriate amount of anhydrous magnesium sulfate drying, filtering to remove the magnesium sulfate anhydrous, removal of the organic solvent under reduced pressure, to obtain darkred brown oily liquid, the liquid after the purification by silica gel chromatography to obtain white crystalline compound e.
General procedure: n-BuLi (4.70mL, 1.6M in hexane, 7.57mmol, 1.0equiv) was added dropwise to a solution of acetylene (7.57mmol, 1.0equiv) in 7.6mL of dry THF at -78C under a nitrogen atmosphere. After 60min at this temperature, trimethylborate (1.10g, 11.3mmol, 1.5equiv) was added dropwise at -30C. The mixture was stirred at this temperature for 60min and slowly allowed to warm to room temperature within another 60min. A saturated 4.5M aqueous solution of potassium hydrogen difluoride (KHF2) (10.1mL, 45.3mmol, 6.0equiv) was added at -20C to the vigorously stirred solution. The resulting mixture was continued to stir for 60min at -20C after which it was allowed to warm to room temperature for 60min. The solvent was removed under reduced pressure, and the resulting white solid was dried under high vacuum to remove water. The solid was washed first with acetone and then with hot acetone. The solution was concentrated to afford a white solid. The solid was dissolved in minimum amount of hot acetone, precipitated by adding methyl tert-butyl ether (MTBE), after which the solution was cooled to -20C to complete precipitation of the solid. The product was collected as an off white solid 2a-o in 40-80% yield.
(3S)-3-(2-azidoacetyloxy)-lup-20(29)-en-28-oic acid[ No CAS ]
[ 10602-03-6 ]
(3S)-3-{2-[4-(4'-ethoxycarbonyl-phenyl)-1H-1,2,3-triazol-1-yl]acetyloxy}-lup-20(29)-en-28-oic acid[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
90%
With copper(II) sulfate; sodium L-ascorbate; In dimethyl sulfoxide; at 20℃; for 2h;Inert atmosphere;
General procedure: Compound 4 (1.0 eqv.) dissolved in dry DMSO (2 mL) was treated with terminal acetylenes 5 (1.1 eqv.) in the presence of sodium ascorbate (1.01 eqv.) and CuSO4*5H2O (1.01 eqv.), and the mixture was stirred at room temperature for 2-18 h under argon atmosphere until the complete consumption of starting materials. It was then purified by silica gel (100-200 mesh) column chromatography using 70-88% ethyl acetate in petroleum ether (v/v) as eluent. The yield was calculated based on the product isolated through column chromatography; however, products screened for anti-cancer assay were further purified by HPLC.
ethyl 4-((2-(hydroxymethyl)phenyl)ethynyl)benzoate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
67%
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; diisopropylamine; In N,N-dimethyl-formamide; at 70℃; for 2h;Inert atmosphere; Schlenk technique;
General procedure: To a mixture of the 2-iodobenzyl alcohol (1.16 g, 5.0 mmol) inDMF (30 mL) were added PdCl2(PPh3)2 (0.70 g, 0.10 mmol), and CuI (0.19 g, 0.10 mmol) under nitrogen. After the reaction mixturewas stirred for 5 min at room temperature, N,N-diisopropylamine(2.02 g, 4.0 equiv) was added by a syringe. The reaction mixturewas then heated at 70 C. A solution of the alkynes (1.2 equiv)in DMF (5 mL) was added dropwise over 10 min, and the mixturewas allowed to stir at 70 C for 2 h. After cooling, the reactionmixture was washed with saturated aq NH4Cl and water, andthen extracted with EtOAc (325 mL). The combinedorganic extracts were dried over MgSO4 and concentrated undervacuum to give the crude product, which was purified by columnchromatography on silica gel using 9:1 to 4:1 hexane/EtOAc aseluent
diethyl 4,4'-(cyclopenta[hi]aceanthrylene-2,7-diylbis(ethyne-2,1-diyl))dibenzoate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
94.3%
With copper(l) iodide; bis(benzonitrile)palladium(II) dichloride; tri-tert-butyl phosphine; diisopropylamine; In toluene; at 50℃; for 48h;Inert atmosphere; Glovebox;
General procedure: In a glovebox were combined 2,7-dibromocyclopenta[hi]aceanthrylene (1 equiv), aryl ethynylene (3 equiv), Pd(PhCN)2Cl2 (6 mol %), and CuI (6 mol %) in a small vial. To these solids were added toluene (4 mL), diisopropylamine (0.8 mL), and PtBu3 (12 mol %). The vial was capped and stirred for 48 h at 50 C. The solvent was removed, and the crude solid was dissolved in a minimal amount of THF and precipitated into cold methanol.
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; In acetonitrile; at 70℃; for 3.33333h;
(2) To a mixture of <strong>[10602-03-6]ethyl 4-ethynylbenzoate</strong> (0.97 g), compound (L1) (1.44 g), acetonitrile (20 mL), and triethylamine (10 mL), dichlorobis(triphenylphosphine)palladium(II) (78.2 mg) and copper(I) iodide (32 mg) were added, and the resulting mixture was heated at 70 C. for 200 minutes. After cooling to room temperature, ethyl acetate (30 mL) and water (30 mL) were added thereto. The organic layer was separated, and the aqueous layer was subjected to extraction with ethyl acetate (30 mL). The organic layers were combined, then washed with water and a saturated aqueous solution of sodium chloride, and dried over anhydrous magnesium sulfate, and then, the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/acetone=20/1 to 10/1) to obtain compound (L2) (1.22 g). TLC Rf: 0.63 (hexane/ethyl acetate=2/1) LC/MS (SunFire) rt (min): 14.63 MS (ESI, m/z): 467.10 [M+H]+
1.22 g
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; In acetonitrile; at 70℃; for 3.33333h;
(2)Ethyl 4-ethynylbenzoate (0.97 g), (L1) (1.44 g),To a mixture of acetonitrile (20 mL) and triethylamine (10 mL)Dichlorobis (triphenylphosphine) palladium (II) (78.2 mg) and copper (I) iodide (32 mg) were added and heated at 70 C. for 200 min.After cooling to room temperature, ethyl acetate (30 mL) and water (30 mL) were added.The organic layer was separated and the aqueous layer was extracted with ethyl acetate (30 mL).The organic layers were combined, washed with water and saturated aqueous sodium chloride solution,After drying over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure,The obtained residue was purified by silica gel column chromatography (hexane / acetone = 20/1 to 10/1) to obtain (L2) (1.22 g).
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; diisopropylamine; In dichloromethane; for 7h;Inert atmosphere; Cooling with ice;
The 1g (1.98 mmol) OPE-1 dissolved in 10 ml of methylene chloride in water-free, adding 396 mg (3.96mmol) diisopropylamine, get colorless solution, the system in the bubble argon parfait under ice bath 20 minutes later, are sequentially added 173 mg (0.99mmol) e, 42 mg (0.06mmol) (triphenylphosphine) palladium chloride, 24 mg (0.12mmol) cuprous share iodizate. 7 hours later, by adding 50 ml methylene chloride after diluting the reaction system, 20 ml adding saturated's amine chloride solution, 20 ml of pure water to wash and saturated 20 ml sodium chloride after washing, collecting the organic phase, and an appropriate amount of anhydrous magnesium sulphate dried for 30 minutes, filtered to remove magnesium sulfate, collecting the organic phase, and the spin vaporization under reduced pressure to remove organic solvent to obtain solid adjustable. The solid after silica gel column of column to obtain white solid (dichloromethane: methanol = 10:1), yield: 81%.
General procedure: To a stirred solution of the appropriate acetylene 11(0.16 mmol) and chlorophosphine gold(l) compound IV (0.16 mmol) in MeOH (2 mL) was added NaOMe (0.5 M in MeOH, 0.18 mmol) dropwise. The formation of a white ppt was observed and the suspension stirred at rtfor 16 h. The pptwas collected by filtration and triturated with MeOH (x 2) and Et20 (x 2), before drying under high vacuum for 18 h to afford the title compound I.:_As Method A except NaOEt was used instead of NaOMe and EtOH instead of MeOH.
With copper(l) iodide; triethylamine; In dichloromethane;Schlenk technique; Inert atmosphere;
General procedure: The complex was synthesized according to modification of a literature method for [Au{RCN(R?)CR}(C?CPh)] [10a,b]. A mixture of [Au{CN{(4-OC12H25)C6H4}C}Cl] (98.9mg, 0.137mmol) (HCN(C6H4-OC12H25-4)CH=4-(4-dodecyloxyphenyl)-2,6-diphenylpyridine) and HC?CC6H4(OCH2CH2)3OMe (36.2mg, 0.137mmol) was stirred in dichloromethane in the presence of catalytic amount of copper(I) iodide and stoichiometric amount of triethylamine. 1 was obtained as a yellow solid.
With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); diisopropylamine; In tetrahydrofuran; at 60℃; for 5h;
To a solution of 10S1 (0.10 g, 0.59 mmol), Pd(PPh3)4 (41 mg, 0.035 mmol), and CuI (34 mg,0.18 mmol) in degassed tetrahydrofuran/diisopropylamine (THF/DIPA) (5/1, v/v) (19 mL) was added2,5-diiodothiophene (DIT) (0.20 g, 0.59 mmol). The solution was stirred at 60 C for 5 h. After coolingto room temperature, the reaction mixture was diluted with dichloromethane and passed through Celiteto remove the metal catalyst. The solution was washed with 1 N HCl aqueous solution and water, andthen dried over Na2SO4. After removing the solvent by evaporation, the crude product was purified bysilica gel chromatography using hexane-dichloromethane (3/2, v/v) as the eluent to give the desiredproduct as a pale yellow solid (62 mg, 27% yield).
With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); diisopropylamine; In tetrahydrofuran; at 60℃; for 5h;
General procedure: To a solution of 10S1 (0.10 g, 0.59 mmol), Pd(PPh3)4 (41 mg, 0.035 mmol), and CuI (34 mg,0.18 mmol) in degassed tetrahydrofuran/diisopropylamine (THF/DIPA) (5/1, v/v) (19 mL) was added2,5-diiodothiophene (DIT) (0.20 g, 0.59 mmol). The solution was stirred at 60 C for 5 h. After coolingto room temperature, the reaction mixture was diluted with dichloromethane and passed through Celiteto remove the metal catalyst. The solution was washed with 1 N HCl aqueous solution and water, andthen dried over Na2SO4. After removing the solvent by evaporation, the crude product was purified bysilica gel chromatography using hexane-dichloromethane (3/2, v/v) as the eluent to give the desiredproduct as a pale yellow solid (62 mg, 27% yield).
6-azido-1,1,4,4-tetramethyl-1,2,3,4-tetrahydronaphthalene[ No CAS ]
[ 10602-03-6 ]
ethyl 4-(1-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)-1H-1,2,3-triazol-4-yl)benzoate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
85%
With copper(ll) sulfate pentahydrate; sodium L-ascorbate; In dichloromethane; water; at 20℃; for 48h;Inert atmosphere;
General procedure: To a solution of the azides (2.2 mmol) and terminalacetylenes (2.0 mmol) in CH2Cl2/H2O (1:1; 4 mL mmol-1),CuSO4.5H2O (0.15 mmol) and sodium ascorbate (0.35 mmol) were added. The mixture was stirred at roomtemperature for 48 h and then extracted with ethyl acetate,the organic phase was dried over anhydrous MgSO4 andthe solvent was removed under vacuum.
tert-butyl (S)-3-(3-amino-5-bromothiophene-2-carboxamido)piperidine-1-carboxylate[ No CAS ]
[ 10602-03-6 ]
tert-butyl (S)-3-(3-amino-5-((4-(ethoxycarbonyl)phenyl)ethynyl)thiophene-2-carboxamido)piperidine-1-carboxylate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
71.5%
With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 100℃; for 12h;
Tert-butyl (S)-3-(3-amino-5-bromothiophene-2-carboxamido)piperidine-1-carboxylate (95.8 mg, 0.190 mmol), 61 <strong>[10602-03-6]ethyl 4-ethynylbenzoate</strong> (30.0 mg, 0.172 mmol), and 43 diisopropylethylamine (38 mg, 0.293 mmol) were dissolved in 44 dimethylformamide (2 mL). 62 Pd(PPh3)4 (9.96 mg, 8.62 umol) and 63 CuI (3.28 mg, 0.017 mmol) were put into the reaction solution, and the resulting mixture was stirred at 100C for 12 hours. The reactant was cooled to room temperature, and then extracted with ethyl acetate and water to collect an organic layer. The collected organic layer was washed with brine solution, dried over sodium sulfate, concentrated under reduced pressure, and purified with MPLC to obtain a target 64 compound (61.3 mg, 71.5 %). MS(m/z): 498 [M+1].
ethyl 1-[(4-methylphenyl)sulfonyl]-2-aziridineacrylate[ No CAS ]
[ 10602-03-6 ]
C25H27NO6S[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
68%
General procedure: To a solution of 5 (0.2 mmol, 1 equiv.) and [Rh(NBD)2]BF4 (5 mol%) in 1,2-DCE (1 mL) was added the corresponding acetylene (0.3 mmol, 1.5 equiv.) in 1,2-DCE (1 mL). The resulting mixture was stirred for 0.5 h. Upon the addition of DABCO (0.1 mmol, 0.5 equiv.), the mixture was heated to 50C for 1 h. The reaction mixture was then quenched with the addition of trifluoroacetic acid (0.3 mmol,1.5 equiv). The solvent was removed under reduced pressure and the residue was purified by columnchromatography using CH2Cl2/hexane as the eluent to give the desired pyrrole 9.
diethyl 4,4'-[(1,2-dimethyl-1H-imidazole-4,5-diyl)]bis(ethyne-2,1-diyl)dibenzoate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
60%
With dichloro bis(acetonitrile) palladium(II); copper(l) iodide; 1,8-diazabicyclo[5.4.0]undec-7-ene; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In N,N-dimethyl-formamide; at 80℃; for 3h;Inert atmosphere;
General procedure: A solution of 4,5-dibromo-1,2-disubstituted-1H-imidazole 2, 7a-e, or 8a (1 mmol) or 5-alkynyl-4-bromo-1,2-dimethyl-1H-imidazole, alkyne 3 (3 mmol or 1.5 mmol), Pd(MeCN)2Cl2 (10 mg, 0.04 mmol, 4 mol%), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (26 mg, 0.04 mmol, 4 mol%), and CuI (3 mg, 0.02 mmol, 2 mol%) in DMF (4.5 mL) and DBU (0.5 mL) was stirred at 80 C for 3 h. The reaction mixture was then diluted with EtOAc (100 mL) and sat. aq NH4Cl (100 mL) was added. The resulting mixture was stirred in the open air for 0.5 h and then extracted with EtOAc. The combined organic extractswere washed with H2O (3 25 mL) and brine (25 mL), dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel. This procedure was employed to prepare 1,2-dimethylimidazole-fused enediynes 5a-e, 2-aryl-1-methylimidazole-fused enediynes 9a-d, and 1,2-diarylimidazole-fused enediyne 10a (Table 2).
ethyl 4-[(4-bromo-1,2-dimethyl-1H-imidazol-5-yl)ethynyl]benzoate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
21%
With 1,1'-bis-(diphenylphosphino)ferrocene; dichloro bis(acetonitrile) palladium(II); copper(l) iodide; 1,8-diazabicyclo[5.4.0]undec-7-ene; In N,N-dimethyl-formamide; at 80℃; for 3h;Inert atmosphere;
General procedure: A solution of 4,5-dibromo-1,2-dimethyl-1H-imidazole (2; 254 mg, 1 mmol), alkyne 3 (1.5 mmol), Pd(MeCN)2Cl2 (10 mg, 0.04 mmol, 4 mol%), 1,1'-bis(diphenylphosphino)ferrocene (22 mg, 0.04 mmol, 4 mol%), and CuI (3 mg, 0.02 mmol, 2 mol%) in DMF (4.5 mL) and DBU (0.5 mL) was stirred at 80 C for 3h. The reaction mixture was then diluted with EtOAc (100 mL) and sat. aq NH4Cl (100 mL) was added. The resulting mixture was stirred in the open air for 0.5 h and then extracted with EtOAc. The combined organic extracts were washed with H2O (3 25 mL) and brine (25 mL), dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel. This procedure was employed to prepare compounds 4a-e (Table 3).
ethyl 4-((2-carbamoyl-4-(trifluoromethyl)phenyl)ethynyl)benzoate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
57%
With bis-triphenylphosphine-palladium(II) chloride; triethylamine; In acetonitrile; at 80℃;Inert atmosphere;
General procedure: To a solution of 2-halobenzamide (2.0 mmol, 1.0 equiv) in MeCN (13 mL) were added PdCl2(PPh3)2 (0.05 equiv), terminal alkyne (1.2 equiv.), and Et3N (3.0 equiv.). The resulting mixture was stirred at 80 C under argon. The progress of the reaction was monitored by TLC analysis to establish completion. After cooling to room temperature, the reaction was diluted with ethyl acetate (30 mL), washed with water (30 mL) and brine (30 mL). The organic phase was dried (anhydrous MgSO4) and concentrated under reduced pressure. The residue was purified by column chromatography (Silica Gel, petroleum ether/ethyl acetate).
4-((7-bromobenzo[c][1,2,5]thiadiazol-4-yl)ethynyl)benzoic acid ethyl ester[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
60%
With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); diisopropylamine; In toluene; at 80℃; for 14h;Inert atmosphere;
S23, 4-ethylethynylbenzoate, 4,7-dibromobenzo [C] [1,2,5] thiadiazole,Tetrakis (triphenylphosphine) palladium and cuprous iodide were added to a clean three-necked flask in a molar ratio of 1: 1.5: 0.05: 0.01.Then dissolve the drug with deoxygenated dry toluene and diisopropylamine (3ml), react at 80 C for 14 hours under nitrogen protection, and then cool to room temperature.Poured into water, extracted the organic phase, and separated by silica gel column chromatography to obtain a milky white solid4-((7-Bromobenzo [c] [1,2,5] thiadiazol-4-yl) ethynyl) benzoate (intermediate product 6), yield 60%.
methyl 3-azido-5-(4-(4-(ethoxycarbonyl)phenyl)-1H-1,2,3-triazol-1-yl)benzoate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
83%
With copper(ll) sulfate pentahydrate; sodium L-ascorbate; tris[(1-benzyl-1H-1,2,3-triazol-4yl)methyl]amine; In tetrahydrofuran; water; tert-butyl alcohol; at 60℃; for 2h;Inert atmosphere;
6 (0.15 g, 0.86 mmol), 7 (1.5 g, 6.9 mmol), and ligand TBTA (91.2 mg, 0.17 mmol) was dissolved in 3:3: 1 THF:/BuOH:H20 solvent mixture (860 mL). The solution was then heated to 60 C and degassed under argon for 30 min, after which CuS045H20 (43 mg, 0.17 mmol), and NaAsc (68 mg, 0.34 mmol) was added. The reaction mixture was stirred under argon for 2 h, then cooled to room temperature, and concentrated in vacuo. The resulting suspension was extracted with dichloromethane. The organic layer was separated, washed with brine, dried over Na2S04, filtered over glass wool, and dried in vacuo. The obtained yellowish solid crude was purified by column chromatography (Si02, 20: 1 to 4: 1 dichloromethane:acetone) to afford 8 (0.28 g, 0.71 mmol) as a white solid. Yield: 83%. 'H NMR (500 MHz, CDCl3), d = 8.35 (s, 1H), 8.15 (d, J= 8.4 Hz, 2H), 8.14 (s, 1H), 7.99 (d, J = 8.2 Hz, 2H), 7.82 - 7.77 (m, 1H), 7.78 (t, J= 2.2 Hz, 1H), 4.41 (q, J= 7.1 Hz, 2H), 4.00 (s, 3H), 1.43 (t, J= 7.1 Hz, 3H). 13C NMR (125 MHz, CDC13), d = 166.16, 164.92, 147.89, 142.81, 138.11, 133.89, 133.46, 130.51, 130.29, 125.67, 119.89, 118.23, 116.84, 115.15, 61.13, 52.90, 14.34. HR-CI-MS: C19H17N6O4 (M+H)+, Calculated: 393.1306; Found: (0329) 393.1383.
2,2‐difluoro‐2‐(triphenylphosphonio)acetate[ No CAS ]
[ 1388753-74-9 ]
Yield
Reaction Conditions
Operation in experiment
75%
With sulfur; potassium fluoride; copper(l) iodide; N,N,N,N,-tetramethylethylenediamine; 4,4'-di-tert-butyl-2,2'-bipyridine; In tetrahydrofuran; at 60℃; for 3h;Sealed tube; Inert atmosphere;
General procedure: In to a 10 ml sealed tube were added alkynes 1 (0.4 mmol), Ph3P+CF2CO2- (570.1 mg, 1.6 mmol), S8 (153.9 mg, 0.6 mmol), CuI (15.2 mg, 0.08 mmol), 4,4?-di-tert-butyl-2,2?-bipyridine (21.5 mg, 0.08 mmol), KF (139.4 mg, 2.4 mmol), TMEDA (92.9 mg, 0.8 mmol) and anhydrous THF (4 mL) under a N2 atmosphere. The tube was sealed and the resulting mixture was stirred at 60 C for 3 h. After being cooled to room temperature, the mixture was filtered through a plug of Celite, and the solid was washed with DCM. The combined organic phase was washed with brine (10 mL * 3) and water (10 mL * 3) and dried with Na2SO4. The solvent was removed by concentration under vacuum, and the residue was subjected to flash column chromatography to give the final products.
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