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CAS No. : | 75867-41-3 | MDL No. : | MFCD14635889 |
Formula : | C13H16O2Si | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | - |
M.W : | 232.35 | Pubchem ID : | - |
Synonyms : |
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Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P280-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302 | Packing Group: | N/A |
GHS Pictogram: |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With hydrogenchloride In methanol | Synthesis of 4-ethynylbenzoic acid 4-(Trimethylsilyl)ethynyl-benzoic acid methyl ester (714 mg, 3.07 mmol) was dissolved in 4percent KOH:MeOH (w:v, 30 mL) and allowed to reflux overnight. The reaction was quenched with 6N HCl to pH 2-3 (as indicated by pH paper) and extracted 2* with EtOAc. The combined organic layers were dried over anhydrous Na2SO4 and evaporated to afford 4-ethynylbenzoic acid (427 mg, 2.92 mmol, 95percent) as a brown solid. 1H-NMR (d6-acetone, 500 MHz) δ (ppm): 7.62 (d, J=16.2 Hz, 2H); 8.03 (d, J=16.3 Hz, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With lithium aluminium tetrahydride In tetrahydrofuran at 0℃; for 0.5 h; Inert atmosphere | [0077] Under argon condition, 4-((trimethylsilyl)ethynyl)benzoic acid methyl ester (316 mg, 1.36 mmol) was dissolvedin 5 mL of dry THF and then cooled to 0 °C and LiAlH4 (2.04 mL, 1.0 M solution in THF, 2.04 mmol) was slowly added thereto. Upon completion of the reaction after stirring for 30 minutes at 0 °C, the reaction was terminated by adding 77 μL of water, 154 μL of 10percent aqueous sodium hydroxide solution and 231 μL of water in order. When the white viscousprecipitate was produced, the mixture was filtered through silica pad to remove the precipitate. The resulting solution was concentrated by distillation under reduced pressure, and purified by column chromatography to obtain 258 mg (1.26mmol, 93percent) of the desired compound.[0078] 1H NMR (300 MHz, CDCl3): d 7.44 (d, 2H, J = 8.2 Hz), 7.27 (d, 2H, J = 8.1 Hz), 4.66 (s, 2H), 1.67 (br, 1H),0.23 (s, 9H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With hydrogenchloride; In methanol; | Synthesis of 4-ethynylbenzoic acid 4-(Trimethylsilyl)ethynyl-benzoic acid methyl ester (714 mg, 3.07 mmol) was dissolved in 4% KOH:MeOH (w:v, 30 mL) and allowed to reflux overnight. The reaction was quenched with 6N HCl to pH 2-3 (as indicated by pH paper) and extracted 2* with EtOAc. The combined organic layers were dried over anhydrous Na2SO4 and evaporated to afford 4-ethynylbenzoic acid (427 mg, 2.92 mmol, 95%) as a brown solid. 1H-NMR (d6-acetone, 500 MHz) delta (ppm): 7.62 (d, J=16.2 Hz, 2H); 8.03 (d, J=16.3 Hz, 2H). |
95% | With hydrogenchloride; | Synthesis of 4-ethynylbenzoic acid. 4-(Trimethylsilyl)ethynyl-benzoic acid methyl ester (714 mg, 3.07 mmol) was dissolved in 4% KOH:MeOH (w:v, 30 mL) and allowed to reflux overnight. The reaction was quenched with 6N HCl to pH 2-3 (as indicated by pH paper) and extracted 2* with EtOAc. The combined organic layers were dried over anhydrous Na2SO4 and evaporated to afford 4-ethynylbenzoic acid (427 mg, 2.92 mmol, 95%) as a brown solid. H-NMR (d6-acetone, 500 MHz) delta (ppm): 7.62 (d, J=16.2 Hz, 2H); 8.03 (d, J=16.3 Hz, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With potassium carbonate In methanol for 2h; | 5j.5; 27.2 Preparation of methyl 4-ethynylbenzoate: Methyl 4-((trimethylsilyl)ethynyl)benzoate (31.5 g, 135.6 mmol) was dissolved in methanol (450 mL). K2CO3 (37.5 g, 271.5 mmol) was added. The mixture was reacted under stirring for 2 hours, and rotary-evaporated to dryness. Ethyl acetate (450 mL) and water (450 mL) were added. The mixture was extracted. The organic phase was dried over anhydrous sodium sulphate, and rotary-evaporated to dryness to give a yellow solid (21.75 g) in a yield of 100%. |
99% | With N,N,N-tributylbutan-1-aminium fluoride In tetrahydrofuran at -20℃; for 0.5h; | |
99% | With potassium carbonate In methanol; dichloromethane |
98% | With potassium carbonate In methanol at 0℃; for 3h; | 45.2 Step 2: Methyl [4-ETHYNYLBENZOATE] (XXXII) To a stirred solution at [0°C] under nitrogen of XXXI (9.05 g, 38.95 [MMOL)] in MeOH (280 ml) was added potassium carbonate (1.62 g, 11.72 [MMOL).] After 3 h, the reaction mixture was concentrated and directly purified by flash chromatography on silica gel [(CH2CI2] : 100) to afford the title compound [XXXII] (6.16 g, 38.46 mmol, 98% yield) as a pale [YELLOW SOLID. 1H] NMR: (400 MHz, [CDCI3)] [8] [(PPM)] : AB system [(JA] = 7.98, AB = 7.54, JAB = 8.6 Hz, 4H), 3.93 (s, 3H), 3.24 (s, 1H). |
98% | Stage #1: 4-trimethylsilanylethynyl-benzoic acid methyl ester With potassium carbonate In methanol at 24.84℃; for 1.5h; Stage #2: With hydrogenchloride In lithium hydroxide monohydrate Inert atmosphere; Schlenk technique; | |
96% | With caesium fluoride In tetrahydrofuran at 20℃; for 3h; Inert atmosphere; | |
95% | With methanol; potassium carbonate In dichloromethane at 20℃; for 2h; Inert atmosphere; | |
95% | With methanol; potassium carbonate In dichloromethane at 20℃; for 1h; | 56.2 (Step 2)The compound obtained in Step 1 (18.30 g, 78.61 mmol) was dissolved in 300 ml of the 2:1 mixture of methanol and dichloromethane, and 5.44 g (39.3 mmol) of potassium carbonate was added. The mixture was stirred at room temperature for 1 hour. At the end of reaction, the reaction mixture was diluted with water and extracted with ethylacetate. The extract was washed with saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and separated by column chromatography to obtain the title compound 11.90 g (Yield 95%). |
95% | With potassium carbonate In methanol at 20℃; for 2h; Inert atmosphere; | 3. Preparation of aryl/alkyl substituted terminal acetylenes 5 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 potassium carbonate In methanol at 25℃; for 3h; | |
94% | With 1,8-diazabicyclo[5.4.0]undec-7-ene In lithium hydroxide monohydrate; acetonitrile at 60℃; for 6.5h; | |
93% | With potassium carbonate In tetrahydrofuran; methanol at 25℃; for 1h; Inert atmosphere; | 2 Preparation of Compound A2-2 Compound A2-1 (250 mg, 1.08 mmol) was dissolved in a mixture of anhydrous THF (7.5 mL) and methanol (7.5 mL), followed by adding K2CO3 to obtain a reaction mixture, which was then subjected to a reaction at 25°C. in a nitrogen atmosphere for 1 hour to obtain a reaction product. The reaction product was added with a saturated aqueous NaHCO3 solution, followed by extraction using methylene chloride to obtain an organic phase. The organic phase was dried using anhydrous sodium sulfate, followed by evacuation to obtain a coarse product. The coarse product was purified by column chromatography on a silica gel column using a 9:1 v/v mixture of n-hexane and ethyl acetate as an eluent to obtain methyl 4-ethynylbenzoate (Compound A2-2 , 160 mg, MW=160.17 g/mole, yield: 93.0%). Spectrum analysis for Compound A2-2: 1H NMR (CDCl3, 300 MHz), δ (ppm): 3.23 (s, 1H); 3.92 (s, 3H); 7.55 (d, 2H, J=8.27 Hz); 7.99 (d, 2H, J=8.27 Hz). 13C NMR (CDCl3, 75 MHz): 52.3, 80.1, 82.8, 129.5, 132.1, 166.4. |
92% | With methanol; potassium carbonate In dichloromethane at 20℃; for 0.833333h; | |
90% | With methanol; potassium hydroxide at 10 - 20℃; for 0.0833333h; | To a solution of methyl 4-((trimethylsiiyl) ethynyljbenzoate (155 g, 0.67 mol) in methanol (800 ml) was added dropwtee KOH/methanoi (18 g/250 mL) keeping the temperature below 1Q°C. The reaction mixture was allowed to warm to room temperature for 5 min and was then neutralized with 2M HCi. Methyl 4- ethynylbenzoate (INT-1.3) was collected by filtration as a w ite solid (97 g( 90%). MS: m z cacd for 01(Η802 160,0, found [M+Hf 161 . |
90% | With methanol; potassium hydroxide at 10 - 20℃; for 0.0833333h; | To a solution of methyl 4-((trimethylsiyl) ethynyl) benzoate (156 g, 0.6/' moL 1.0 equiv) in methanol (800 mL) was added dropwise KOH/methanol (18 g/250 mL) keeping the temperatur below 100C, the mixture was allowed to warm to room temperature for 5 min. The reaction mixture was neutralized with 2M HCL The reactio suspension was filtered to collect methyl 4~ethynyibenzoate (INT-1.3) as a white solid (97 g, 90%). MS: m/z calcd for C10HsO2 160.0, found [M+Hf 161. |
90% | With potassium hydroxide In methanol at 10 - 20℃; | To a solution of methyl4-((trimethylsilyl) ethynyl) benzoate(156 g, 0.67 mol, 1.0 equiv) in methanol (800 ml)was added dropwise KOH/methanol (18 g/250 ml)keepingthetemperaturebelow 10°C, the mixture was allowed to warm to room temperature for 5 min. The reaction mixture was neutralized with 2M HCI. Thereaction suspension was filtered to collect methyl 4-ethynylbenzoate (INT-1.3) as a white solid (97 g, 90%). MS: m/z calcd for C10H802160.0, found [M+Ht161. |
90% | With N,N,N-tributylbutan-1-aminium fluoride In tetrahydrofuran at -20℃; for 3h; | Methyl 4-(ethynyl)benzoate (10) [5] Methyl 4-(2-trimethylsilylethynyl)benzoate (9) (3 g, 12.9 mmol) wasdissolved in 20 mL THF and cooled to -20 °C with acetone/dry ice. TBAF (1 M solution, 15 mL) wasadded during stirring. After 3 h, water (50 mL) was added and the phases were separated. Theaqueous phase was washed with diethyl ether (3 × 50 mL) and the organic phases combined, washedwith brine and dried over MgSO4. Solvents were evaporated and the crude product was purified bycolumn chromatography (pentane/EtOAc 5:1) to give ester 10 as dark yellow solid (1.9 g, 11.9 mmol,90%). Rf = 0.90 (n-pentane/EtOAc = 4:1). |
89% | With methanol; potassium carbonate In dichloromethane at 20℃; for 3h; | |
89% | With potassium carbonate In methanol at 20℃; for 3h; Inert atmosphere; | Synthesis of methyl 4-ethynylbenzoate Methyl 4-((trimethylsilyl)ethynyl)benzoate (10.00g), K2CO3 (15.00 g), and methanol (150 mL) were added into a 250 mL round-bottom flask. The reaction mixture was stirred under nitrogen at room temperature for 3 h. The mixture was then filtered, and the solution was neutralized with hydrochloric acid to adjust the pH between 3~4. The obtained precipitates were washed by distilled water and dried under vacuum with yield of 89%. δ H (400 MHz, CDCl3): 7.99 (2 H, d), 7.55 (2 H, d), 3.92 (3H, s), 3.23 (1H, s). δ C (101 MHz, CDCl3): 166.4, 132.1, 130.1, 129.5, 126.7, 82.8, 80.1, 52.3. |
89% | With potassium carbonate In methanol for 0.166667h; | |
87% | With N,N,N-tributylbutan-1-aminium fluoride In tetrahydrofuran at 20℃; for 0.166667h; | |
87% | With methanol; potassium carbonate In dichloromethane at 20℃; for 24h; Inert atmosphere; | |
85.4% | With N,N,N-tributylbutan-1-aminium fluoride In tetrahydrofuran at 20℃; Inert atmosphere; Schlenk technique; | |
84% | With methanol; potassium carbonate at 20℃; for 3h; Inert atmosphere; | |
84% | With sodium hydroxide In methanol; diethyl ether at 20℃; for 0.25h; | |
81% | With anhydrous sodium carbonate In methanol at 20℃; for 3h; | |
80% | With methanol; potassium carbonate at 20℃; for 3h; Inert atmosphere; | 1 3: The silylatealkyne compound starting material (7.9 g, 34 mmol) is dissolved in anhydrous MeOH (150 mL), and then potassium carbonate (23.46 g, 170 mmol, 5 equiv) is added. The mixture is stirred for 3h under argon at room temperature. The mixture is added to water (150 mL) to quench the reaction. The mixture is extracted with diethyl ether (3x100 mL), and then the combined organic extracts are dried over anhydrous Na2SO . The solvent is evaporated in vacuum to afford the crude product, which is purified by chromatography (eluting with 25-30% DCM in hexane) to afford 3 (4.4 g, 80% yield) as brown solid. 1 H NMR (300 MHz, CDCI3) 53.23(s, 1 H), 3.91 (s, 3H), 7.54 (d, J=8.7 Hz, 2H), 7.98 (d, J=8.7 Hz, 2H); 13C NMR (75 MHz, CDCI3) 552.20, 80.31 , 83.01 , 126.96, 129.68, 130.34, 132.30, 166.63; LC/MS m/s [M+H]+ 161 .2. |
78% | With N,N,N-tributylbutan-1-aminium fluoride In tetrahydrofuran at 20℃; for 0.166667h; | |
76% | With N,N,N-tributylbutan-1-aminium fluoride In tetrahydrofuran at 20℃; for 3h; Inert atmosphere; | 5.B B) Methyl 4-ethynylbenzoate To a solution of methyl 4-((trimethylsilyl)ethynyl)benzoate (1.35 g, 5.35 mmol) in THF (10 mL) was added TBAF (1 M solution in THF, 10.7 mL, 10.70 mmol). The resulting brown reaction mixture was stirred at rt for 3 h and concentrated in vacuo. The residue was purified by flash column chromatography (eluting with 5% EtOAc/hexane) to afford the title compound as a white solid (0.65 g, 76%). 1H NMR (CDCI3) δ 8.00 (d, J= 8.6 Hz, 2H), 7.56 (d, J= 8.6 Hz, 2H), 3.93 (s, 3H), 3.23 (s, 1H). |
76% | With potassium carbonate In methanol at 20℃; for 1h; Sealed tube; Inert atmosphere; | |
75% | With methanol; potassium carbonate at 25℃; for 6h; | |
75% | With ethanol; potassium carbonate at 20℃; for 1h; | 1 Synthesis of intermediate (3) Add 1.25 g of Intermediate 2 to a 50 mL double-neck flask, then add 1.2 g of potassium carbonate (12 mmol) and 0 ml of absolute ethanol, react at room temperature for 1 hour, and pass the crude product through silica gel column chromatography to obtain a solid of 720 mg, with a yield of 75%. |
73.1% | With potassium carbonate In methanol at 25℃; for 3h; | |
73% | With methanol; potassium carbonate In dichloromethane at 20℃; for 3h; | Methyl 4-[2'-(trimethylsilyl)ethynyl]benzoate obtained above (7.9 g, 34 mmol) was dissolved in anhydrous MeOH (150 mL) and dichloromethane (DCM, 150 mL), and potassium carbonate (23.46 g, 170 mmol, 5 equiv) was added. The mixture was stirred at room temperature for 3 h. The reaction was quenched by water (150 mL), and the resulting mixture was extracted with diethyl ether (3×100 mL), and then the combined organic extracts were dried. The solvent was concentrated in vacuo to afford the crude product, which was purified by chromatography (eluting with 25-30% DCM in hexane) to afford methyl 4-ethynylbenzoate 4 (4.0 g, 73% yield) as brown solid. 1H NMR (300 MHz, CDCl3): δ 3.23(s, 1H), 3.90 (s, 3H), 7.53 (d, J=8.7 Hz, 2H), 7.98 (d, J=8.7 Hz, 2H); 13C NMR (75 MHz, CDCl3): δ 52.19, 80.31, 83.01, 126.96, 129.68, 130.343, 132.30, 166.62; MS (ESI, positive): m/z 233 [M+H]+. |
73% | With methanol; potassium carbonate In dichloromethane for 18h; Inert atmosphere; | |
70% | With potassium carbonate In methanol; dichloromethane at 20℃; for 1h; Schlenk technique; Inert atmosphere; | |
67% | With potassium carbonate In tetrahydrofuran; methanol at 20℃; for 1h; Inert atmosphere; | |
64% | With methanol; potassium carbonate for 4h; | |
64% | With N,N,N-tributylbutan-1-aminium fluoride In tetrahydrofuran at -20℃; for 0.5h; | |
60% | With methanol; potassium carbonate In dichloromethane for 3h; Ambient temperature; | |
51% | With potassium carbonate In methanol for 1.5h; | |
With N,N,N-tributylbutan-1-aminium fluoride In tetrahydrofuran for 0.333333h; | ||
0.49 g | With potassium carbonate In methanol; dichloromethane at 20℃; for 2h; | |
With methanol; potassium carbonate at 20℃; for 24h; | ||
11.7 g | With N,N,N-tributylbutan-1-aminium fluoride In tetrahydrofuran at 20℃; for 1h; Inert atmosphere; | |
With potassium carbonate In methanol at 20℃; for 3h; | ||
With potassium carbonate In methanol at 20℃; | ||
With methanol; potassium hydroxide In lithium hydroxide monohydrate at 0 - 25℃; for 12h; Darkness; Inert atmosphere; | ||
With methanol; potassium fluoride | ||
With methanol; potassium carbonate In dichloromethane at 20℃; for 2h; | ||
With methanol; potassium carbonate at 0℃; for 3h; | I26.1 Intermediate 26; Example I26.1; General Route; 4-Ethynyl-benzoic acid methyl ester; 18.1 g (77.9 mmol) 4-trimethylsilanylethynyl-benzoic acid methyl ester are added to 400 mL MeOH, cooled down to 0° C. and charged with 3.24 g (23.4 mmol) K2CO3. The reaction mixture is stirred for 3 h, then the solvent is removed in vacuo and the resulting residue is purified by column chromatography (silica gel, hexane/TBME 10/1).C10H8O2 (M=160.2 g/mol)EI-MS: 160 [M]+ Rf (TLC): 0.7 (silica gel, CyH/EtOAc 2/1) | |
With potassium carbonate In methanol | ||
With methanol; potassium carbonate In dichloromethane at 20℃; for 12h; Inert atmosphere; Schlenk technique; | ||
0.99 g | With anhydrous sodium carbonate In methanol at 20℃; for 3h; Inert atmosphere; | |
With N,N,N-tributylbutan-1-aminium fluoride In tetrahydrofuran at 20℃; for 2h; | 21 Synthesis of Compound B 11 The crude intermediate 1 was dissolved treated with TBAF in THF (20 mL. 20 mmol) at r.t. for 2 hours then quenched by water and extracted with EtOAc (50 mL x 2). The combine organic layer was dried over anhydrous Na2SO4 concentrated to give crude intermediate 2 which was puritied by column chromatography to give 2 (0.9 g, 58%) as yellow solid. | |
0.9 g | With N,N,N-tributylbutan-1-aminium fluoride In tetrahydrofuran at 20℃; for 2h; | 21 The crude intermediate 1 was dissolved treated with TBAF in THF (20 mL, 20 mmol) at r.t. for 2 hours, then quenched by water and extracted with EtOAc (50 mL×2). The combine organic laser was dried over anhxdrous Na2SO4, concentrated to give crude intermediate 2 which was purified by column chromatography to give 2 (0.9 g, 58%)) as yellow solid. 1H NMR (300 MHz, DMSO-d6) δ7.96 (d, 2H), 7.62 (d, 2H), 4.48 (s, 1H), 3.87 (s, 3H), |
With methanol; potassium carbonate at 20℃; for 3h; | ||
With methanol; potassium carbonate at 20℃; for 3h; Inert atmosphere; Schlenk technique; | ||
11.1 g | With potassium carbonate In methanol; dichloromethane for 6h; Inert atmosphere; | 2.2.c 2(c) Methyl 4-ethynylbenzoate (7) To a MeOH:DCM solution (2: 1, 300 mL) was added 6 (18.5 g, 79.5 mmol) and K2CO3 (22.0 g, 159 mmol). The mixture was stirred under Ar for 6 h. The solution was then evaporated to 1/3 volume, diluted with hexane, passed through Celite and evaporated to give a light brown solid, which was purified by sublimation under reduced pressure to give 7 as a white solid (11.1 g, 83% over two steps): 1H NMR (600 MHz, CDCI3) δ 3.23 (s, 1H), 3.91 (s, 3H), 7.54 (d, J = 8.4 Hz, 2H,), 7.98 (d, J = 8.6 Hz, 2H); 13C NMR (176 MHz, CDC13) δ 52.5, 80.2, 83.0, 126.9, 129.6, 130.3, 132.3, 166.6; IR (neat) v^/cm-1 3035w, 3006w, 2950w, 2103w, 1699s, 1605m, 1433m, 1277s, 1107s, 859s; MS (GC): m/z = 160.1 [M]+; Found: C, 74.62; H, 5.01. Calc. for C10H8O2: C, 74.99; H, 5.03%. |
With potassium carbonate In methanol at 20℃; for 3h; Inert atmosphere; | ||
With potassium carbonate In tetrahydrofuran; methanol at 20℃; for 24h; | ||
With N,N,N-tributylbutan-1-aminium fluoride In tetrahydrofuran at 0℃; for 0.5h; Inert atmosphere; | ||
With potassium carbonate at 20℃; for 1h; Inert atmosphere; | Methyl 4-ethynylbenzoate (V-25) To a solution of V-13 (739 mg, 3.185 mmol) in anhydrous THF (10 mL), K2CO3 (660 mg, 4.778 mmol) was added under argon. The solution was stirred at room temperature for 1 h. The solvent was removed under reduced pressure. The resulting mixture was extracted with ethyl acetate and the organic phase was washed with water and brine, dried over anhydrous Na2SO4, filtered and then the filtrate was concentrated in vacuo to give 380 mg (74.6%) of V-25 as a white solid, used for the next step without further purification. MS (EI) m/z: (M+, 160). | |
With potassium carbonate In methanol at 20℃; | ||
With potassium carbonate In methanol at 25℃; for 6h; | ||
With N,N,N-tributylbutan-1-aminium fluoride; glacial acetic acid In tetrahydrofuran | R.46 Reference Example 46 Reference Example 46 4-ethynyl-benzoic acid methyl ester. To a solution of 4-trimethylsilanylethynyl-benzoic acid methyl ester (4.65 g, 20 mmol) (reference example 47) in THF (40 mL) is added (1M) tetrabutylammonium fluoride (3 mL, 30 mmol) and acetic acid (1.9 mL, 33 mmol). The resulting solution is stirred for 25 min, diluted with ethyl acetate, washed with water and brine, dried over MgSO4 and concentrated. The residue is purified by flash chromatography (eluding with 10% ether, 10% dichloromethane in hexanes) to give 2.56 g of title compound as a pale yellow solid. 1H NMR (CDCl3) δ 3.23 (s, 1H), 3.92 (s, 3H), 7.55 (d, J=8 Hz, 2H), 8.00 (d, J=8 Hz, 2H). MS (EI) m/z 160 (M+). | |
With methanol; potassium carbonate at 25℃; for 6h; | ||
With potassium carbonate In methanol at 20℃; for 2h; | Methyl 4-ethynyl benzoate (9) In a round-bottom flask, Compound 7 (1 eq) was dissolved in anhydrous THF, and a catalytic amount of ditriphenylphosphorus palladium dichloride and cuprous iodide, and triethylamine (2 eq) and trimethylsilylacetylene (2 eq) were added, the mixture was stirred at 50 °C for 18 h under the nitrogen atmosphere; then the reaction was filtered with diatomaceous earth, water and ammonia were added, and extracted with ethyl acetate; After the organic phase was dried, the solvent was removed almost quantitatively to obtain compound 8; compound 8 was directly dissolved in methanol without further purification, added anhydrous potassium carbonate, stirred at room temperature for 2 hours, and then removed methanol, added water and ethyl acetate for extraction , Compound 9 was distributed in the organic phase and obtained compound 9 as a white solid (yield 88%) after removing the solvent; 1H NMR (400 MHz, Chloroform-d) δ 7.99 (d, J = 8.7 Hz, 2H), 7.55 (d, J = 8.4 Hz, 2H), 3.92 (s, 3H), 3.23 (s, 1H). 13C NMR (100 MHz, CDCl3) δ 166.45, 132.12, 130.22, 129.50, 126.81, 82.85, 80.05, 52.30. | |
With methanol; potassium carbonate at 20℃; for 1h; | ||
With potassium carbonate In tetrahydrofuran; methanol at 20℃; for 12h; Inert atmosphere; Schlenk technique; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; diethylamine; triphenylphosphine In N,N-dimethyl-formamide at 120℃; for 0.416667h; Microwave irradiation; Inert atmosphere; | Methyl 4-(2-trimethylsilylethynyl)benzoate (9) [4] Methyl 4-bromobenzoate (8) (1.5 g, 7 mmol), PPh3(0.37 g, 1.4 mmol), Pd(PPh3)2Cl2 (0.3 g, 0.42 mmol), CuI (0.08 g, 0.42 mmol), trimethylsilyl acetylene(1.1 mL, 7.7 mmol), Et2NH (10 mL, 98 mmol) and DMF (4 mL) was added to a 10-20 mL Biotechmicrowave vial. The mixture was heated by microwave irradiation to 120 °C for 25 min under N2atm. and stirring. The reaction mixture was diluted with diethyl ether and treated with 1 M HCl. Thephases were separated and the aqueous phase washed with diethyl ether (3 × 30 mL). The combinedorganic phases were washed with saturated NaHCO3 solution, water and brine. Solvents wereevaporated to give crude black oil that was treated with pentane and filtered through celite.Evaporation of the filtrate gave ester 9 with high purity as bright orange solid (1.47 g, 6.33 mmol,98%). |
96% | With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine at 90℃; for 0.5h; Inert atmosphere; | Eth nytfime hyisfiane (82.4 g, 0,84 mol) was added dropwise over 10 min under a nitrogen atmosphere to a solution of methyl 4-bromobenzoate (150 g, 0.7 mol), PdC (PPh3)2 (15 g, 0.021 mol) and Cu (13 g, 0.07 mol) in TEA (1.5 L) and the reaction was siirsd at 90 for 30 minutes. Solids were collected by filtration and washed with EtOAc (5 x 500 mL). The filtrate was concentrated under reduced pressure to give a residue, which was distilled under reduced pressure to yield methyl 4-C(trimethylsify) ethynyl) benzoate (INT-12) as an off-white solid (156 g, 96%), |
96% | With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine at 90℃; for 0.5h; Inert atmosphere; | EthynyHrimethylsilane (82.4 g. 0.84 rnol. 1.2 equiv) was added dropwise over 10 min under a nitrogen atmosphere to a soiution of methyl 4-brornobenzoate (150 g, 0.7 mol 1.0 equiv), PdC2 iPP h), (15 g, 0.021 mot.. 0.03 equiv) and Cul (13 g, 0.068 mol, 0.1 equiv) in TEA (1.5 L), The reaction was stired at 90°C for 30 minutes, whereupon LCMS showed complete consumption of methyl 4-bromobenzoate. Then, the reaction mixture was filtered and the filter cake was washed with EiOAe (5 x 500 rnLj, The filtrate was concentrated under reduced pressure to give a residue, which was distilled under reduced pressure to yield methyl 4~{{triroethyi8tiyi) ethynyl) benzoate (INT-1.2) as an off-white solid (156 g, 96%). |
96% | With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine at 90℃; for 0.5h; Inert atmosphere; | Ethynyltrimethylsilane (82.4 g, 0.84 mol, 1.2 equiv) was added dropwise over 10 min under a nitrogenatmosphere to a solution of methyl4-bromobenzoate(150 g, 0.7mol1.0equiv), PdCb (PPh3h (15 g, 0.021 mol, 0.03 equiv) and Cui (13 g, 0.068mol, 0.1 equiv) in TEA20 (1.5 L). The reaction was stired at 90°C for 30 minutes,whereupon LCMS showed completeconsumption of methyl 4-bromobenzoate. The reaction mixture wasfiltered and the filter cake was washed with EtOAc (5 x 500 ml). The filtrate was concentrated under reduced pressure togive a residue, which was distilledunder reduced pressure to yield methyl 4-((trimethylsilyl) ethynyl)benzoate (INT-1.2) as an off-white solid (156 g, 96%). |
95% | With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; triphenylphosphine at 50℃; for 18h; Inert atmosphere; | |
94% | With triethylamine In tetrahydrofuran at 0 - 20℃; | 45.1 Example 45 N-(2-AMINOPHENYL-4-[3-(1,3-DIHYDR-ISOINDOL-2-YL-PROPENYL]BENZAMIDE (XXXA) Step 1: METHYL 4-TRIMETHYLSILANYLETYNYLBENZOATE (XXXI) A stirred solution at room temperature of methyl 4-bromobenzoate (8.84 g, 41.11 [MMOL),] Pd [(PPH3)] 2Cl2 (840 mg, 1.20 [MMOL)] and Cul (455 mg, 2.39 [MMOL)] in anhydrous THF (200 ml) was saturated with nitrogen for 15 min. Then, the solution under nitrogen was cooled down at [0°C,] and [TRIMETHYLSILYLACETYLENE] (7.2 [ML,] 50.91 [MMOL)] and triethylamine (22 [ML,] 157.8 [MMOL)] were added successively. The reaction mixture was allowed to warm up at room temperature. After 2 h, Pd [(PPH3)] 2Cl2 (100 mg) and Cul (80 mg) and trimethylsilylacetylene (0.5 ml) were added again, and the reaction mixture was stirred overnight. Then, the reaction mixture was diluted with AcOEt and successively washed with a saturated aqueous solution of NH4CI and brine, dried over [MGS04,] filtered and concentrated. The crude residue was then purified by flash chromatography on silica gel (AcOEt/hexane: [5/95010/90)] to afford the title compound XXXI (9.05 g, 38.95 [MMOL,] 94% yield) as a yellow sticky [SOLID. 1H] NMR: (400 MHz, CDCl3) 8 [(PPM)] : AB system [(8A] = 7.67, AB = 7.22, JAB = 8.5 Hz, 4H), 3.63 (s, 3H), 0.00 (s, 9H). |
93% | Stage #1: 4-methoxycarbonylphenyl bromide; trimethylsilylacetylene With bis-triphenylphosphine-palladium(II) chloride; triethylamine; triphenylphosphine In tetrahydrofuran at 20℃; for 0.333333h; Inert atmosphere; Stage #2: With copper(l) iodide In tetrahydrofuran at 20℃; for 15h; Inert atmosphere; | 1.1.β.1 Step 1: Synthesis of 4-((trimethylsilyl)ethynyl)benzoic acid methyl ester Under argon condition, 4-bromobenzoic acid methyl ester (500 mg, 2.33 mmol), bis(triphenylphosphine)palladium dichloride (Pd(PPh3)2Cl2; 86.1 mg, 0.116 mmol), triphenylphosphine (PPh3; 18.3 mg, 0.0698 mmol), trimethylsilyl acetylene (TMS acetylene; 493 μL, 3.49 mmol), and triethylamine (Et3N; 486 μL, 3.49 mmol) were dissolved in 10 mL of well-dried tetrahydrofuran (dry THF) and stirred for 20 minutes at room temperature. To this was added again cuprous iodide (CuI; 8.86 mg, 0.0465 mmol) and the reaction mixture was stirred for 15 hours at room temperature. Upon completion of the reaction, the solvent was removed by distillation under reduced pressure, and 20 mL of n-pentane was added to the residue. The mixture was filtered through celite pad to remove the precipitate. The resulting solution was concentrated by distillation under reduced pressure and purified by column chromatography to obtain 503 mg (2.16 mmol, 93%) of the desired compound. 1H NMR (300 MHz, CDCl3): d 7.93 (dd, 2H, J = 6.8 Hz, J = 1.7 Hz), 7.48 (dd, 2H, J = 6.7 Hz, J = 1.8 Hz), 3.88 (s, 3H), 0.22 (s, 9H). |
92% | With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triphenylphosphine In tetrahydrofuran; triethylamine Heating; | |
92% | With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine at 50℃; for 24h; | |
91% | With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); triethylamine for 24h; Inert atmosphere; Reflux; | |
90.4% | With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In tetrahydrofuran at 60℃; for 5h; | Methyl 4-((trimethylsilyl) ethynyl) benzoate (V-13) A mixture of V-01 (922 mg, 4.292 mmol), ethynyltrimethylsilane (506 mg, 5.153 mmol), Pd(PPh3)2Cl2 (150 mg, 0.214 mmol), CuI (25 mg, 0.131 mmol), TEA (1.73 g, 17.16 mmol) was dissolved in anhydrous THF (20 mL). The mixture was stirred at 60 for 5 h. The solvent was removed under reduced pressure. The residue was partitioned between ethyl ether and water. The organic layer was washed with water and brine, dried over anhydrous Na2SO4, filtered and then the filtrate was concentrated in vacuo. The residue was purified by silica gel chromatography with PE/EA (50/1-20/1) to give 0.9 g (90.4%) of V-13 as a brown oil. 1H NMR (400 MHz, Chloroform-d) δ 7.99 (d, J = 8.4 Hz, 2H), 7.54 (d, J = 8.3 Hz, 2H), 3.94 (s, 3H), 0.28 (s, 9H). MS (EI) m/z: (M+, 233). |
89% | With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide In triethylamine for 4h; Ambient temperature; | |
70% | With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine at 85℃; for 24h; Inert atmosphere; | |
69% | With palladium diacetate; triethylamine; triphenylphosphine at 100℃; for 4h; | |
34% | With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); diisopropylamine In acetonitrile at 70 - 80℃; for 4h; | |
With triethylamine In tetrahydrofuran for 4h; Heating; | ||
262.2 mg | With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triphenylphosphine In diethylamine; N,N-dimethyl-formamide at 120℃; for 0.416667h; microwave irradiation; | |
20.8 g | With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In acetonitrile at 50℃; for 24h; Inert atmosphere; | |
With triethylamine In tetrahydrofuran; cyclohexane; ethyl acetate | 14 Synthesis of 4-(trimethylsilyl)ethynyl-benzoic acid methyl ester Synthesis of 4-(trimethylsilyl)ethynyl-benzoic acid methyl ester 4-Bromobenzoic acid methyl ester (1.124 g, 5.22 mmol), PdCl2(PPh3)2 (192 mg, 27.4 mmol), and PPh3 (37 mg, 14.1 mmol) were suspended in THF (25.0 mL). Ethynyltrimethylsilane (1.14 mL, 8.1 mmol) and Et3N (1.14 mL, 7.8 mmol) were added and the reaction was allowed to stir for 20 min. CuI (14 mg, 0.075 mmol) was added and the reaction color changed from orange to red. Reaction was allowed to proceed overnight. After overnight reaction, the solution was brown in color and TLC analysis indicated the reaction was complete. The reaction mixture was concentrated to a brown residue, redissolved in DCM and filtered through Celite. The filtrate and rinses were evaporated to dryness and purification via Silica in 15:1 cyclohexane:EtOAc afforded 4-(trimethylsilyl)ethynyl-benzoic acid methyl ester (656 mg, 2.82 mmol, 54%) as an orange solid. 1H-NMR (CD3Cl, 500 MHz) δ (ppm): 0.239 (s, 9H); 3.89 (s, 3H); 7.49 (d, J=16.84 Hz, 2H); 7.94 (d, J=16.4 Hz, 2H). | |
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In 1,4-dioxane at 100℃; Inert atmosphere; | 21 Synthesis of Compound B 11 To a solution of SM1 (2.1g, 10 mmol) in dioxane (20 mL) was added ethynyltrimethylsilane (2g, 20 mmol), CuI (191 mg, 1 mmol) and Pd(PPh3)2CI2 (730 mg, 1mmol) under N2 then Et3N (10 g, 100 mmol) was added dropwise. After stirred at 100oCovernight the mixture was quenched by water extracted with EtOAc (50 mL x 2). The combine organic layer was dried over anhydrous Na2S04 concentrated to give crude intermediate 1. | |
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In 1,4-dioxane at 100℃; Inert atmosphere; | 21 To a solution of SM1 (2.1 g, 10 mmol) in Dioxane (20 mL) was added ethynltrimethylsilane (2 g, 20 mmol), CuI (191 mg, 1 mmol) and Pd(PPH3)2Cl2 (730 mg, 1 mmol) under N2, then Et3N (10 g, 100 mmol) was added dropwise. After stirred at 100 oC overnight, the mixture was quenched by water, extracted with EtOAc (50 mL×2). The combine organic layer was dried over anhydrous Na2SO4, concentrated to give crude intermediate 1. | |
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In tetrahydrofuran at 20℃; for 24h; Schlenk technique; | ||
With triethylamine In tetrahydrofuran; cyclohexane | 14 Example 14 Synthesis of 4-(trimethylsilyl)ethynyl-benzoic acid methyl ester. 4-Bromobenzoic acid methyl ester (1.124 g, 5.22 mmol), PdCl2(PPh3)2 (192 mg, 27.4 mmol), and PPh3 (37 mg, 14.1 mmol) were suspended in THF (25.0 mL). Ethynyltrimethylsilane (1.14 mL, 8.1 mmol) and Et3N (1.14 mL, 7.8 mmol) were added and the reaction was allowed to stir for 20 min. CuI (14 mg, 0.075 mmol) was added and the reaction color changed from orange to red. Reaction was allowed to proceed overnight. After overnight reaction, the solution was brown in color and TLC analysis indicated the reaction was complete. The reaction mixture was concentrated to a brown residue, redissolved in DCM and filtered through Celite. The filtrate and rinses were evaporated to dryness and purification via Silica in 15:1 cyclohexane: EtOAc afforded 4-(trimethylsilyl)ethynyl-benzoic acid methyl ester (656 mg, 2.82 mmol, 54%) as an orange solid. H-NMR (CD3C1, 500 MHz) δ (ppm): 0.239 (s, 9H); 3.89 (s, 3H); 7.49 (d, J=16.84 Hz, 2H); 7.94 (d, J=16.4 Hz, 2H). | |
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine for 12h; Inert atmosphere; | ||
Stage #1: 4-methoxycarbonylphenyl bromide With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine for 0.166667h; Stage #2: trimethylsilylacetylene at 50℃; for 4h; | ||
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine at 50℃; for 18h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With triethylamine In tetrahydrofuran at 20℃; for 8h; | 56.1 (Step 1)20.60 g (78.61 mmol) of 4-Iodobenzoic acid methyl ester and 9.26 g (94.33 mmol) of ethynyl trimethylsilane were dissolved in 200 ml of tetrahydrofuran, and thereto 23.86 g (235.83 mmol) of triethylamine, 1.65 g (2.36 mmol) of dichloro(bistriphenylphosphine)palladium(II) and 0.45 g (2.36 mmol) of cupper(I) iodide were added. The mixture was stirred at room temperature for 8 hours. At the end of reaction, added water and extracted with ethylacetate. The extract was washed with saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and separated by column chromatography to obtain trimethylsilylethynylbenzoic acid methyl ester 18.30 g (Yield 100%). |
100% | With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine; triphenylphosphine In N,N-dimethyl-formamide at 20℃; for 3h; Inert atmosphere; | |
98% | With copper (I) iodide; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 60℃; for 18h; |
98% | With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine In tetrahydrofuran at 20℃; | |
98.5% | With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine In tetrahydrofuran at 50℃; for 20h; Glovebox; Schlenk technique; | 2 Preparation of Compound A2-1 Methyl 4-iodobenzoate (1 g, 3.816 mmol), trimethylsilylacetylene (5 mL, 35.13 mmol, 9.24 equiv.), and triethylamine (15 mL) were added into a Schlenk flask, followed by addition of anhydrous THF (15 mL) as a solvent to obtain a mixture. The mixture was degassed using a freeze/thaw cycle (three times), and was then added with Pd(PPh3)2Cl2 (133.94 mg, 5 mol %) and copper (I) iodide (CuI, 36.34 mg, 5 mol %) within a water-free and oxygen-free glove box to obtain a reaction mixture, which was subjected to a reaction in an oil bath at 50°C. for 20 hours to obtain a reaction product. The reaction product was concentrated under reduced pressure to remove THF and triethylamine, and was dissolved in a proper volume amount of methylene chloride, followed by extraction using NH4Cl(aq) in a volume amount equal to that of methylene chloride to obtain an organic phase. The organic phase was dried using anhydrous sodium sulfate, followed by evacuation to obtain a coarse product. The coarse product was purified by column chromatography on a silica gel column using a 9:1 v/v mixture of n-hexane and ethyl acetate as an eluent to obtain methyl 4-trimethylsilyl ethynyl benzoate (Compound A2-1 , 878 mg, MW=232.35 g/mole, white solid, yield: 98.5%). Spectrum analysis for Compound A2-1: 1H NMR (CDCl3, 300 MHz), δ (ppm): 0.25 (s, 9H); 3.90 (s, 3H); 7.50 (d, 2H, J=8.43 Hz); 7.95 (d, 2H, J=8.43 Hz). 13C NMR (CDCl3, 75 MHz): -0.2, 52.2, 97.7, 104.1, 127.8, 129.4, 129.7, 131.9, 166.5. |
98% | Stage #1: methyl 4-iodobenzoate With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine In tetrahydrofuran at 20℃; for 0.0833333h; Inert atmosphere; Stage #2: trimethylsilylacetylene In tetrahydrofuran at 20℃; for 18h; Inert atmosphere; | |
98% | With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine In N,N-dimethyl-formamide at 20℃; Inert atmosphere; | 3. Preparation of aryl/alkyl substituted terminal acetylenes 5 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. |
97% | With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 20℃; for 2h; | |
97% | With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine; triphenylphosphine In N,N-dimethyl-formamide at 20℃; for 2h; Inert atmosphere; | |
97% | With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 20℃; for 4h; Inert atmosphere; | |
97% | With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine In N,N-dimethyl-formamide at 50℃; for 1h; Inert atmosphere; Sealed tube; | |
96% | With piperidine at 20℃; for 2h; | |
96% | With copper (I) iodide; tetrakis-(triphenylphosphine)-palladium; triethylamine In tetrahydrofuran at 0 - 20℃; Inert atmosphere; | |
96% | With copper (I) iodide; tetrakis-(triphenylphosphine)-palladium; triethylamine In toluene at 20℃; for 3h; Inert atmosphere; | 5.B B) Methyl 4-ethynylbenzoate To a solution of methyl 4-iodobenzoate (1.5 g, 5.72 mmol) and trimethylsilylacetylene (Aldrich, 1.58 mL, 11.45 mmol) in toluene (12 mL) were added Pd(PPh3) 4 (0.66 g, 0.57 mmol), Cul (0.16 g, 0.86 mmol), and TEA (6.4 mL, 45.80 mmol). The resulting reaction mixture was purged with nitrogen for 3 min and stirred at rt for 3 h. The reaction mixture was diluted with ethyl acetate and NH4C1 solution. Theorganic layer was separated, washed with brine, dried over MgS04 and concentrated in vacuo. The residue was purified by flash column chromatography (eluting with 10% EtOAc/hexane) to afford the title compound as a white solid (1.35 g, 96%). 1H NMR (CDC13) δ 7.98 (d, J= 8.6 Hz, 2H), 7.53 (d, J= 8.6 Hz, 2H), 3.92 (s, 3H), 0.27 (s, 9H); MS(ESI+) m/z 233.1 (M+H)+. |
95% | With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine In tetrahydrofuran at 80℃; for 1.5h; | |
95% | With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine; N,N-diisopropylamine at 80℃; for 8h; Inert atmosphere; | |
94% | With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 80℃; for 12h; Inert atmosphere; | |
94% | Stage #1: methyl 4-iodobenzoate With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; trimethylamine In tetrahydrofuran for 0.0833333h; Schlenk technique; Inert atmosphere; Stage #2: trimethylsilylacetylene In tetrahydrofuran at 24.84℃; Schlenk technique; Inert atmosphere; | |
90% | With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine | |
90% | With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triphenylphosphine In triethylamine at 20℃; Inert atmosphere; | |
89% | With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 20℃; for 2h; | |
89% | With copper (I) iodide; tetrakis-(triphenylphosphine)-palladium; triethylamine at 20℃; Inert atmosphere; Schlenk technique; | |
89% | With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine; triphenylphosphine In 1,4-dioxane at 20℃; for 4h; Schlenk technique; Inert atmosphere; | |
89% | With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine In toluene at 80℃; for 24h; Inert atmosphere; | |
88% | With copper (I) iodide; triethylamine; triphenylphosphine; palladium (II) chloride In acetonitrile for 3h; Heating; | |
88% | Stage #1: methyl 4-iodobenzoate With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine In acetonitrile at 20℃; for 0.5h; Inert atmosphere; Stage #2: trimethylsilylacetylene In acetonitrile at 20 - 100℃; for 18h; Inert atmosphere; Sealed tube; | Synthesis of CH-90 To a solution of compound 1 (10g, 38.2 mmol) in acetonitrile was added triethylamine (15.4g, 153 mmol) followed by copper(I) iodide (145 mg, 0.76 mmol) and Pd(PPh3)2Cl2 (268 mg, 0.38 mmol) at room temperature under argon atmosphere. The reaction mixture was purged with argon for 30 min. To this solution was added TMS acetylene (3.74 g, 38.2 mmol) at room temperature and the reaction vessel was closed tightly (Sealed tube). The reaction mass was heated to 100 oC and maintained for 18 h. The reaction mixture was cooled to room temperature and diluted with water (200 mL). The resulting solution was extracted with ethyl acetate (100 mL x 3). The combined organic layer was washed with water (200 mL), brine solution (100 mL), dried over anhydrous MgSO4 and evaporated under reduced pressure to get crude compound 2. The crude product was purified by filter column (Silica gel, 100-200 mesh) using 1% ethyl acetate in pet-ether as mobile phase to yield pure compound 2 (7.5 g, 88%). 'H NMR (400 MHz, CDCl3-d3) 7.95-7.96(d, 2H), 7.5(d, 2H), 3.9(s, 3H), 0.25 (s, 9H) ppm |
88.9% | With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine In tetrahydrofuran for 18h; Inert atmosphere; | 5j.4; 27.1 Preparation of methyl 4-((trimethylsilyl)ethynyl)benzoate: Methyl 4-iodobenzoate (40 g, 152.6 mmol), trimethylsilylethyne (14.99 g, 152.6 mmol), triethylamine (35.47 g,350.5 mmol), Pd(PPh3)2Cl2 (1.071 g, 1.526 mmol) and CuI (0.291 g, 1.526 mmol) were dissolved in THF (300 mL). The atmosphere was replaced with nitrogen gas three times. The mixture was stirred at normal temperature for 18 hours, rotary-evaporated to dryness, and purified by silica column chromatography (100%petroleum ethers→petroleum ether:ethyl acetate=1:2) to give a red solid (31.5 g) in a yield of 88.9%. |
86% | With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine In tetrahydrofuran at 20℃; for 16h; | |
85% | With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 60℃; for 22h; Inert atmosphere; | 4-[(4'-Aminophenyl)buta-1,3-diyn-1-yl]benzoic acid (6). To an oven-dried round-bottom flask equipped with a condenser and a magnetic stir bar was added methyl 4-iodobenzoate (10.48 g, 40 mmol), bis(triphenylphosphine) palladium (II) dichloride (1.404 g, 2.0 mmol, 0.05 equiv) and copper (I) iodide (0.076 g, 4 mmol, 0.10 equiv). The flask was then sealed with a rubber septum under argon, and anhydrous THF (100 mL) and diisopropylethylamine (28 mL, 160 mmol, 4 equiv), and (trimethylsilyl)acetylene (8 mL, 52 mmol, 1.3 equiv) was added sequentially. The reaction mixture was heated to 60 °C on an oil bath for 22 h. The resulting dark solution was concentrated under reduced pressure. The residue was treated with water (100 mL), and extracted with ethyl acetate (EtOAc) (3×100 mL). The combined extracts were washed with water (50 mL), brine (50 mL) and dried (anhydrous Na2SO4). The crude products were purified by CombiFlash (eluting with 50-60% DCM in hexane) to afford methyl 4-[2'-(trimethylsilyl)-ethynyl]benzoate (7.9 g, 85%) as yellow solid. 1H NMR (300 MHz, CDCl3): δ 0.25 (s, 9H), 3.90 (s, 3H), 7.50 (d, J=8.7 Hz, 2H), 7.96 (d, J=8.7 Hz, 2H); 13C NMR (75 MHz, CDCl3): δ 0.05, 52.43, 79.90, 104.28, 127.98, 129.60, 129.89, 132.09, 166.71; MS (ESI, positive): m/z 255 [M+Na]+. |
85.1% | With N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 60℃; for 22h; Inert atmosphere; Sealed vessel; | 1 Exam le 12: To an oven-dried round bottom flask equipped with water cooled west condenser and magnetic stir bar are added Methyl 4-iodobenzoate (10.48 g, 40 mmol), bis triphenylphosphine) palladium (II) dichloride (1 .404 g, 2.0 mmol, 0.05 equiv) and copper (I) iodide (0.076 g, 4 mmol, 0.10 equiv.). The vessel is then sealed with a rubber septum under argon and are added anhydrous THF (100 mL) and diisopropylethylamine (28 mL, 160 mmol, 4 equiv). Finally, the (trimethylsily) acetylene (8 mL, 52 mmol, 1 .3 equiv) is added and the reaction mixture is heated by oil at 60 C for 22h. The resulting dark solution is condensed to dryness with a rotavapor, and the residue is treated with water (100 mL), extracted with EtOAc (3x100 mL). The combined extracts are washed with water (50 mL) and brine (anhydrous Na2SO4). The crude products are purified by flash chromatography (eluting with 50-60% DCM in hexane) to afford 2 (7.9 g, 85.1 %) yellow solid. 1 H NMR (300 MHz, CDCIs) 50.25 (s, 9H), 3.90 (s, 3H), 7.51 (d, J=8.7 Hz, 2H), 7.96 (d, J=8.7 Hz, 2H); 13C NMR (75 MHz, CDCI3) δ 0.06, 52.44, 79.90, 104.28, 127.98, 129.60, 129.90, 132.09, 166.71 ; LC/MS m/s [M+Na]+ 255.1 . |
84% | Stage #1: methyl 4-iodobenzoate; trimethylsilylacetylene With triethylamine In tetrahydrofuran for 0.166667h; Stage #2: With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide In tetrahydrofuran at 80℃; for 4h; Inert atmosphere; | |
83% | Stage #1: methyl 4-iodobenzoate With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine In tetrahydrofuran at 20℃; for 0.166667h; Inert atmosphere; Stage #2: trimethylsilylacetylene In tetrahydrofuran at 20℃; for 20h; Inert atmosphere; | |
82% | With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; 1,8-diazabicyclo[5.4.0]undec-7-ene In toluene at 20℃; for 24h; Inert atmosphere; | |
82% | With copper (I) iodide; tetrakis-(triphenylphosphine)-palladium; triethylamine; triphenylphosphine at 20℃; for 3h; Inert atmosphere; | |
75% | With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); triethylamine In tetrahydrofuran at 20℃; for 16h; Inert atmosphere; | Synthesis of methyl 4-((trimethylsilyl)ethynyl)benzoate [1] Methyl 4-iodobenzoate (19.65 g), CuI (0.45 g), and Pd(PPh3)2Cl2 (0.53 g) were added into a 500 mL round-bottom flask, and then the system was evacuated and purged with N2 for three times. After that, dry THF (50 mL), triethylamine (150 mL) and ethynyltrimethylsilane (7.37 g) were added. The resulting solution was stirred under nitrogen at room temperature for 16 h. The mixture was then filtered, and the solution was dried by rotary evaporation. The obtained residue was recrystallized with ethanol. The white solid with yield of 75% was finally got. δ H (400 MHz, CDCl3): 7.97 (2 H, d), 7.52 (2 H, d), 3.91 (3 H, s), 0.26 (9 H, s). δ C (101 MHz, CDCl3): 166.7, 132.0, 129.9, 129.5, 127.9, 104.2, 97.8, 52.4, 0.2. |
75% | With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 75℃; for 12h; | |
72% | With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 80℃; for 4h; Inert atmosphere; | |
69% | With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine In tetrahydrofuran at 50℃; for 16h; Reflux; Inert atmosphere; | |
64% | With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine In diethylamine at 20℃; for 18h; | |
64% | With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine In tetrahydrofuran at 80℃; for 18h; Inert atmosphere; | 2 4 Synthesis of [(trimethylsilyl)ethynyl]benzoic acid methyl ester (110) The compound obtained in the above Step 1(109) (2.03 g) was dissolved in THF (16 mL), PdCl 2 (PPh 3) 2 (267 mg), CuI (145 mg), triethylamine (4 mL), trimethylsilylacetylene (1.49 g) was added, under an argon atmosphere, and the mixture was stirred for 18 hours at 80 ° C. The reaction mixture was filtered, filtrate was concentrated under reduced pressure, the residue was purified by silica gel flash column chromatography (developing solvent n-hexane:ethyl acetate = 10: 1) to obtain the compound (110) (1.89 g, 64% yield ) as a yellow solid. |
59.6% | With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine for 48h; Inert atmosphere; Reflux; | |
89 % Chromat. | With copper (I) iodide; triethylamine In tetrahydrofuran at 20℃; | |
With copper (I) iodide; triethylamine In tetrahydrofuran at 21℃; | ||
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine; triphenylphosphine at 60℃; for 30h; Inert atmosphere; | ||
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine In N,N-dimethyl-formamide at 120℃; for 0.0833333h; Microwave irradiation; | ||
Stage #1: methyl 4-iodobenzoate With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triphenylphosphine In tetrahydrofuran at 25℃; for 0.166667h; Inert atmosphere; Stage #2: trimethylsilylacetylene With triethylamine In tetrahydrofuran at 25℃; for 12h; Inert atmosphere; | ||
With copper (I) iodide; tetrakis-(triphenylphosphine)-palladium; N,N-diisopropylamine In tetrahydrofuran | ||
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine In tetrahydrofuran at 60℃; Inert atmosphere; | ||
With triethylamine | ||
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine In tetrahydrofuran at 20℃; for 12h; Inert atmosphere; Schlenk technique; | ||
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 20℃; for 2h; Schlenk technique; | ||
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 60℃; for 12h; Inert atmosphere; | ||
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 20℃; Inert atmosphere; Sealed tube; Schlenk technique; | 2.2.b 2(b) Methyl 4-((trimethylsilyl)ethynyl)benzoate (6) An oven-dried 500 mL Schlenk flask was evacuated under reduced pressure and refilled with Ar, before Pd(PPh3)2Cl2 (1.18 g, 1.68 mmol), Cul (1.68 g, 1.68 mmol) and 5 (22.0 g, 83.98 mmol) were added and the flask sealed with a septum. Triethylamine (200 mL) and trimethylsilylacetylene (13.94 mL, 100.8 mmol) were added and the flask evacuated/filled with Ar again (3x). The mixture was stirred at RT overnight. The solution was diluted with hexane, passed through Celite/SiCh under vacuum, and evaporated to give 6 as an off-white solid (19.8 g). This was carried to the next step without purification: MS (GC): m/z = 232.1 [M]+; Found: C, 66.90; H, 6.88. Calc. for C13H1602Si: C, 67.2; H, 6.94%. | |
0.26 g | With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine Heating; | Methyl 4-((trimethylsilyl) ethynyl) benzoate (5): A suspension of p-iodo methylbenzoate (0.30 g, 1.14 mmol), TMS-acetylene (0.24 mL, 1.71 mmol), Pd(PPh3)2Cl2 (0.02 g, 0.03 mmol) and CuI (0.013 g, 0.07 mmol) in a 2:1 mixture of deoxygenated Et3N (4 mL) and THF (2 mL) in a pressure tube was heated while stirring at 80 °C overnight. The reaction was filtered through celite and solid residue was washed three times with ether. Filtrate was concentrated and the crude residue purified by column using Hexanes:EtOAc (20:1) to give compound 5 as a brown solid (0.26 g, 99 %). 1H NMR (400 MHz, CDCl3) δ 7.99 (d, 2H), 7.52 (d, 2H), 7.33 - 7.28 (m, 1H), 3.89 (s, 3H), 0.28 - 0.20 (s, 9H). 13C NMR (101 MHz, CDCl3) δ 166.4, 131.8, 129.7, 129.3, 127.7, 104.0, 97.5, 52.2, -0.3. |
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine In tetrahydrofuran | ||
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine In tetrahydrofuran at 80℃; for 2h; Inert atmosphere; | ||
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; N,N-diisopropylamine at 60℃; for 1h; Sealed tube; Inert atmosphere; | ||
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 75℃; for 12h; | ||
With n-butyllithium In tetrahydrofuran | R.47 Reference Example 47 Reference Example 47 4-trimethylsilanylethynyl-benzoic acid methyl ester. To a cooled solution (-78° C.) of (trimethylsilyl)acetylene (4.2 mL, 30 mmol) in THF (25 mL) is added dropwise (2.5M) n-butyllithium (11.6 mL, 29 mmol) and stirred for 30 min followed by slow addition of (0.5M) zinc chloride (58 mL, 29 mmol). The resulting solution is allowed to warm to 20° C. followed by addition of 4-iodo-benzoic acid methyl ester (5.24 g, 20 mmol) (reference example 48) and tetrakis(triphenylphosphine)palladium(0) (1.16 g, 1 mmol) in THF (10 mL). The resulting mixture is heated to 55° C. and stirred for 2 hours then cooled to 20° C. The reaction mixture is diluted with ethyl acetate, washed with sat.NH4Cl soln, water and brine, dried over MgSO4 and concentrated to give 4.65 g of title compound. 1H NMR (CDCl3) δ 0.26 (s, 2H), 3.91 (s, 3H), 7.52 (d, J=8 Hz, 2H), 7.97 (d, J=8 Hz, 2H). MS (EI) m/z 232 (M+). | |
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 75℃; for 12h; | ||
With copper (I) iodide; trans-bis(triphenylphosphine)palladium(II) dichloride | ||
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine In tetrahydrofuran at 50℃; | General procedure (Sonogashira click): In a first round-bottom flask, iodophenyl starting material was dissolved in THF(10 mL per 4 mmol). Ethynyltrimethylsilane (1.1 equiv), triethylamine(4 equiv), PdCl2(PPh3)2 (0.4 mol%), and CuI (0.4mol%) were then added, and the mixture was stirred at 50 °C until completion of the Sonogashira reaction. In a second round-bottom flask, fluoronitrobenzene starting material (1.05equiv) was dissolved in MeCN (10 mL per 4 mmol). Sodium azide (1.15 equiv) and tetrabutylammonium hydrogensulfate (0.05 equiv) were then added and the mixture was stirred at 50 °C until completion of the aromatic nucleophilic substitutionreaction. The first round-bottom flask was then filtrated, andthe filtrate was poured into the second round-bottom flask. CuI (8 mol%) was finally added, and the resulting mixture was stirred at 60 °C until completion of both the deprotection and click reaction. The resulting solution was then filtered over Celite, and the filtrate was evaporated under reduced pressure. Recrystallization with EtOH was performed to obtain the desired product. Analytical data for a representative compound obtained by this procedure: Methyl 4-[1-(5-chloro-2-nitrophenyl)-1H-1,2,3-triazol-4-yl]benzoate: 1H NMR (400 MHz, DMSO-d6): = 3.88(s., 3 H, CH3), 7.85-8.08 (overlapping signals, 5 H, HAr), 8.18-8.39 (overlapping signals, 2 H, HAr), 9.36 (s, 1 H, Htriazole). 13CNMR (126 MHz, DMSO-d6): = 52.0 (CH3), 124.0 (CH, CAr), 125.3(CH, CAr), 127.2 (CH, CAr), 127.2 (CH, CAr), 129.1 (Cq, CAr), 129.8(Cq, CAr), 129.9 (CH, CAr), 131.0 (CH, CAr), 134.0 (Cq, CAr), 138.4(Cq, CAr), 142.4 (Cq, Ctriazole), 145.8 (Cq, CAr), 165.7 (Cq, C=O).HRMS (ESI): m/z [M + H]+ calcd for C16H12N4O4Cl: 359.0542;found: 359.0532. | |
Stage #1: methyl 4-iodobenzoate With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine at 20℃; for 0.5h; Schlenk technique; Inert atmosphere; Stage #2: trimethylsilylacetylene at 20℃; for 4h; Schlenk technique; Inert atmosphere; | ||
1.25 g | With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; ethylamine; triphenylphosphine for 2h; | 1 Synthesis of intermediate (2) Add 1.83g of methyl p-iodobenzoate into a 50mL round bottom two-necked bottle,Then add 12mL ethylamine, add 40mg cuprous iodide, 75mg triphenylphosphine and 35mg ditriphenylphosphine palladium dichloride, add 0.05ml trimethylsilylacetylene, and react for 2h. It was extracted with ethyl acetate, and the solvent was removed under reduced pressure to obtain 1.25 g of white solid. |
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine In tetrahydrofuran at 50℃; for 18h; Inert atmosphere; | Methyl 4-ethynyl benzoate (9) In a round-bottom flask, Compound 7 (1 eq) was dissolved in anhydrous THF, and a catalytic amount of ditriphenylphosphorus palladium dichloride and cuprous iodide, and triethylamine (2 eq) and trimethylsilylacetylene (2 eq) were added, the mixture was stirred at 50 °C for 18 h under the nitrogen atmosphere; then the reaction was filtered with diatomaceous earth, water and ammonia were added, and extracted with ethyl acetate; After the organic phase was dried, the solvent was removed almost quantitatively to obtain compound 8; compound 8 was directly dissolved in methanol without further purification, added anhydrous potassium carbonate, stirred at room temperature for 2 hours, and then removed methanol, added water and ethyl acetate for extraction , Compound 9 was distributed in the organic phase and obtained compound 9 as a white solid (yield 88%) after removing the solvent; 1H NMR (400 MHz, Chloroform-d) δ 7.99 (d, J = 8.7 Hz, 2H), 7.55 (d, J = 8.4 Hz, 2H), 3.92 (s, 3H), 3.23 (s, 1H). 13C NMR (100 MHz, CDCl3) δ 166.45, 132.12, 130.22, 129.50, 126.81, 82.85, 80.05, 52.30. | |
With triethylamine In tetrahydrofuran at 20℃; for 12h; Schlenk technique; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With lithium aluminium tetrahydride; In tetrahydrofuran; at 0℃; for 0.5h;Inert atmosphere; | [0077] Under argon condition, 4-((trimethylsilyl)ethynyl)benzoic acid methyl ester (316 mg, 1.36 mmol) was dissolvedin 5 mL of dry THF and then cooled to 0 C and LiAlH4 (2.04 mL, 1.0 M solution in THF, 2.04 mmol) was slowly added thereto. Upon completion of the reaction after stirring for 30 minutes at 0 C, the reaction was terminated by adding 77 muL of water, 154 muL of 10% aqueous sodium hydroxide solution and 231 muL of water in order. When the white viscousprecipitate was produced, the mixture was filtered through silica pad to remove the precipitate. The resulting solution was concentrated by distillation under reduced pressure, and purified by column chromatography to obtain 258 mg (1.26mmol, 93%) of the desired compound.[0078] 1H NMR (300 MHz, CDCl3): d 7.44 (d, 2H, J = 8.2 Hz), 7.27 (d, 2H, J = 8.1 Hz), 4.66 (s, 2H), 1.67 (br, 1H),0.23 (s, 9H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 81 percent / sodium carbonate / methanol / 3 h / 20 °C 2: 91 percent / Pd(PPh3)2Cl2; CuI; triethylamine / 2 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: 81 percent / sodium carbonate / methanol / 3 h / 20 °C 2: 46 percent / Pd(PPh3)2Cl2; CuI; triethylamine / 20 °C 3: 0.26 g / NaOH / methanol / 24 h / Heating | ||
Multi-step reaction with 3 steps 1.1: potassium carbonate; methanol / dichloromethane / 3 h / 20 °C 2.1: triethylamine / 0.17 h 2.2: 50 °C / Inert atmosphere 3.1: potassium hydroxide / tetrahydrofuran; water; methanol / 85 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
28 mg | With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; 1,8-diazabicyclo[5.4.0]undec-7-ene; triethylamine In water; N,N-dimethyl-formamide at 120℃; for 0.25h; Microwave irradiation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
10 g | With sodium hydroxide In ethanol at 20℃; for 18h; | Synthesis of CH-90 To a solution of compound 2 (13 g, 56 mmol) in ethanol was added sodium hydroxide 4.5 g, 112 mmol) at room temperature and the reaction mixture was stirred at the same temperature for 18 h. The solvent was removed under reduced pressure and the residue was washed with pentane to get crude compound 3 as sodium salt. The crude product was taken to the next step as a sodium salt without further purification (10 g, crude).LC-MS m/z 145.2 (M-l). MW = 146.15 amu 'H NMR (400 MHz, DMSO-d6) 7.84-7.86(d, 2H), 7.40-7.42(d, 2H), 4.22(s, 1H) ppm |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: cesium fluoride / tetrahydrofuran / 3 h / 20 °C / Inert atmosphere 2: triphenylphosphine; copper(l) iodide; triethylamine; bis-triphenylphosphine-palladium(II) chloride / 1,4-dioxane / 96 h / 115 °C / Inert atmosphere; Sealed tube 3: sodium hydroxide / water; ethanol / 24 h / Reflux |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With cobalt acetylacetonate In acetonitrile at 80℃; for 12h; Sealed tube; regioselective reaction; | Typical Procedure for a Cobalt-Catalyzed [3+2] Regioselective Annulation of Ortho-Formyl and Acetyl Phenylboronic Acids with Alkynes: General procedure: A 25 mL sealed tube equipped with a magnetic stirring bar was charged with Co(acac)2 (0.05 mmol, 10 mol%), DPPE (0.05 mmol, 10 mol%), ortho-formylphenylboronic acid 1a (0.75 mmol, 1.5 equiv), an alkyne 2d (0.50 mmol, 1.0 equiv), and MeCN (2 mL). The reaction mixture was stirred at 80 °C for 12 h. The mixture was then filtered through silica gel pad. The filtrate was concentrated, and the residue was purified by column chromatography on silica gel to yield the desired product 3d as a yellow solid in 72% yield (121.6 mg, 0.359 mmol) |
Tags: 75867-41-3; Methyl 4-((trimethylsilyl)ethynyl)benzoate;
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P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
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