* 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.
With potassium hydroxide In tetrahydrofuran; water at 20℃; for 2 h;
Compound 4 (727 mg, 3.6 mmol) was dissolved in 15 mL of anhydrous THF and 2 mL of aqueous KOH solution was added(298 mg, 4 mmol), reacted at room temperature for 2 h. The THF was spin-dried. The reaction was extracted with EA and washed three times with saturated NaCl solution.The organic phase was dried over anhydrous Na2SO4, filtered, concentrated, and purified by column chromatography with PE and DCM (1:1 by volume) to give 450 mg of compound 5 as a pale yellow solid. The yield is 97percent.
94%
at 20℃; for 2 h;
B. 4-ethynylbenzaldehyde; A degassed solution of 4-bromobezaldehyde (6.0 g, 32.4 mmol) and triphenylphosphine (0.17 g, 0.65 mmol) in 60 mL of anhydrous triethylamine was added ethynyltrimethylsilane (26.7 mL, 48.6 mmol) followed by palladium (II) acetate (0.072 g, 0.32 mmol) at room temperature under argon atmosphere. The reaction mixture was heated at reflux for 2 h in sealed tube. The reaction mass was cooled to room temperature and the precipitated solid was filtered. The filtrate was concentrated to provide crude compound. The crude compound was purified by column chromatography (silica gel, 100-200 mesh) by using 1percent ethyl acetate in pet-ether as mobile phase to provide 4- ((trimethylsilyl)ethynyl)benzaldehyde (5.2 g, 80percent). This compound was taken up in methanol (100 mL), to which potassium carbonate (0.341 g, 2.47 mmol) was added at room temperature. The reaction mass was stirred for 2 h. The solvent was removed under reduced pressure and the residue was diluted with dichloromethane (50 mL). The organic solution was washed with water (50 mL), brine solution (25 mL), dried over anhydrous magnesium sulfate and evaporated under reduced pressure to get 4-ethynylbenzaldehyde as light brown solid (3.0 g, 94percent).LC-MS: [M+H]+ 131.2 Mass: calculated for C9H6O, 130.15IH NMR (400 MHz, δ ppm, CDC13): δ 10.02 (s, IH), 7.85 (d, 2H), 7.65 (d, 2H), 3.29 (s, IH)
90%
With potassium hydroxide In methanol; dichloromethane at 20℃; for 6 h;
4-((Trimethylsilyl)ethynyl)benzaldehyde (2.0 g, 10.0 mmol) and KOH (561 mg, 10.0 mmol) were dissolved in the mixed solvents of CH2Cl2 (10 mL) and MeOH (5 mL). The mixture was stirred at room temperature for 6 h, and then the solvent was concentrated under reduced pressure. H2O (20 mL) and CH2Cl2 (20 mL) were added to the obtained residue to afford a two-phase solution. The aqueous layer was extracted with CH2Cl2 (2 × 20 mL), and the combined organic layers were washed with H2O, and then dried over MgSO4. The solution was filtered, and the solvent was removed by rotary evaporation to give a light yellow powder identified as 4-ethynylbenzaldehyde 2 (1.17 g, 90percent). 1H NMR (300 MHz, CDCl3) δ 10.01 (s, 1H), 7.86-7.81 (m, 2H), 7.63 (d, J = 8.2 Hz, 2H), 3.32 (s, 1H). ESI-MS: m/z: 129.17 [M − H]−.
85.5%
With potassium carbonate In methanol; dichloromethane; Petroleum ether
This compound (8.00 g, 39.59 mmol) was treated with K2CO3 (0.500 g) in methanol (50 mL) at 25° C. for 2 hours under Argon. The solvent was removed under vacuum, and the residue was dissolved in dichloromethane (100 mL). This solution was washed once with a saturated aqueous NaHCO3 solution, and once with water, was then dried over anhydrous Na2SO4, and the solvent was evaporated under vacuum. The yellow residue was purified by column chromatography using dichloromethane/petroleum ether 1:4, and then recrystallized from cold cyclohexane to give 4.40 g (85.5percent yield) of the title compound; MS (EI) m/e 130.0; (M+). 1H-NMR (CDCl3) δ ppm: 3.30 (s, 1H, CH), 7.64 (d, 2H, ArH, J=8.1 Hz), 7.84 (d, 2H, ArH, J=8.1 Hz), 10.02 (s, 1H, CHO).
85.5%
With potassium carbonate In methanol; dichloromethane; Petroleum ether
This compound (8.00 g, 39.59 mmol) was treated with K2CO3 (0.500 g) in methanol (50 mL) at 25° C. for 2 hours under Argon. The solvent was removed under vacuum, and the residue was dissolved in dichloromethane (100 mL). This solution was washed once with a saturated aqueous NaHCO3 solution, and once with water, was then dried over anhydrous Na2SO4, and the solvent was evaporated under vacuum. The yellow residue was purified by column chromatography using dichloromethane/petroleum ether 1:4, and then recrystallized from cold cyclohexane to give 4.40 g (85.5percent yield) of the title compound; MS (El) m/e 130.0; (M+). 1H-NMR (CDCl3) δ ppm: 3.30 (s, 1H, CH), 7.64 (d, 2H, ArH, J=8.1 Hz), 7.84 (d, 2H, ArH, J=8.1 Hz), 10.02 (s, 1H, CHO).
85.5%
With potassium carbonate In methanol at 25℃; for 2 h;
This compound (8.00 g, 39.59 mmol) was treated with K2CO3 (0.500 g) in methanol (50 mL) at 25 C. for 2 hours, under Argon. The solvent was removed under vacuum and the residue dissolved in dichloromethane (100 mL). This solution was washed once with an aqueous saturated solution of NaHCO3 and once with water, before being dried over anhydrous Na2SO4 and the solvent evaporated under vacuum. The yellow residue was purified by column chromatography using dichloromethane/petroleum ether 1:4 for elution and recrystallization from cold cylohexane to give 4.40 g (85.5percent yied) of the title compound; MS (EI) m/e 130.0; (M+). 1H-NMR (CDCl3) ? ppm: 3.30 (s, 1H, CH), 7.64 (d, 2H, ArH, J=8.1 Hz), 7.84 (d, 2H, ArH, J=8.1 Hz), 10.02 (s, 1H, CHO).
85%
at 20℃; for 24 h;
A deaerated solution of 4-bromobenzaldehyde (3, 4.87 g, 25 mmol),triphenylphosphine (0.33 g, 1.25 mmol), PdCl2 (45 mg, 0.25 mmol), and Cu(OAc)2 (48 mg, 0.25 mmol) inanhydrous triethylamine (60 mL) was treated with trimethylsilylacetylene (5.5 mL, 38 mmol). The mixture wasbrought to reflux for 6 h. After cooling, the precipitated triethylamine hydrobromide was filtered off, and thesolvent was evaporated. The crude material was purified by silica gel column chromatography (silica gel 120 g,hexanes/ethyl acetate = 90/10), affording 4-((trimethylsilyl)ethynyl)benzaldehyde (4.49 g, 89percent yield) as a yellowsolid. 4-((Trimethylsilyl)ethynyl)benzaldehyde (4.05 g, 20 mmol) was treated with K2CO3 (2.28 mg, 2 mol) inMeOH (24 mL) at room temperature for 24 h. The solvent was removed in vacuo. The crude material was purifiedby silica gel column chromatography (silica gel 120 g, hexanes/ethyl acetate = 90/10), affording 4-ethynylbenzaldehyde (5; 2.20 g, 85percent yield) as a yellow solid.
84%
With potassium carbonate In methanol at 20℃; for 24 h;
To a mixture of PdCl2(PPh3)2 (175 mg, 0.3 mmol) andCuI (190 mg, 1.0 mmol) in THF (30 mL), 4-bromobenzaldehyde (1.85 g, 10 mmol), trimethylsilyl acetylene(1.12 mL, 12 mmol), and NEt3 (10 mL) were added.The resulted mixture was stirred for 24 h at room temperature.The solvent was removed and 30 mL CH2Cl2 wasadded. The mixture was washed with water (3 30 mL). Theorganic phase was dried with MgSO4 and the solvent wasremoved by rotary evaporation. Purification by columnchromatography (Silica gel, CH2Cl2/hexane 1:2) gave 4-(2-(trimethylsilyl)ethynyl) -benzaldehyde derivative as whitesolid (yield 85percent).To a stirred solution of 4-(2-(trimethylsilyl)ethynyl) benzaldehyde(5 mmol) in CH3OH (30 mL), K2CO3 (69 mg, 0.5mmol) was added. The mixture was stirred for 24 h at roomtemperature, and the solvent was removed. The residue wasdiluted with 30 mL Et2O and washed with water (3 30mL). The organic phase was dried over MgSO4 and the solventwas removed by rotary evaporation. Purification by aflash colum chromatography (Silica gel, Et2O) provide 5 aswhite solid (546 mg, yield 84percent).1H NMR (400 MHz, CDCl3) 10.04 (s, 1H), 7.87 (d, J =8.0, 2H), 7.67 (d, J = 8.0, 2H), 3.32 (s, 1H).
81%
With potassium carbonate In methanol at 20℃; for 1 h;
A solution of 545 4-((trimethylsilyl)ethynyl)benzaldehyde (7.5 g, 37.12 mmol) in 124 methanol (100 mL) was charged with 63 potassium carbonate (512 mg, 3.712 mmol) and stirred at room temperature for 1 h. The reaction mixture was concentrated in vacuo, diluted with ethyl acetate and separated organic layer was washed with water. The separated organic layers were dried over anhydrous Na2SO4, filtered and concentrated in vacuo resulting in the crude 543 compound which was purified by column chromatography on silica gel eluting with 0-20percent ethyl acetate in n-hexane to afford 1.2 g, 81percent yield, of the title compound as light yellow solid. 1H NMR (400 MHz, CDCl3) δ=10.02 (s, 1H), 7.85 (d, J=7.83 Hz, 2H), 7.64 (d, J=8.31 Hz, 2H), 3.30 (s, 1H).
75%
at 20℃; for 3 h;
A solution of p-bromobenzaldehyde (2 mmol, 370 mg)Was dissolved in 15 ml of anhydrous triethylamine,Vacuum,Replaced with argon three times,Weigh Pd (PPh3) 2Cl2 (0.06 mmol, 43 mg)PPh3 (0.06 mmol, 16 mg),CuI (0.02 mmol, 4 mg) was added.Then, 0.5 ml of trimethylsilylacetylene was injected.Heated to 70 degrees,The reaction was carried out for 6 hours and after cooling to room temperature,Filter out a white solid,Wash the filter cake several times with CH2Cl2.The solvent was removed under reduced pressure.Silica gel column.The resulting brown solid was then dissolved in methanol,K2CO3 (2 mmol, 390 mg)Room temperature reaction for 3 hours,Filter K2CO3,Pressurized to remove methanol,Over silica gel column,EluentFor petroleum ether: dichloromethane (1: 1),To obtain 195 mg,The yield was 75percent.
72%
at 25℃; for 1 h;
To a solution of 4-Trimethylsilanylethynyl-benzaldehyde (4.0 g, 19.7 mmol) in methanol (50 mL) was added K2CO3 (275 mg, 1.97 mmol) at 25 °C. The reaction mixture stirred at same temperature over a period of 60 min. Methanol was evaporated to the half volume at 35 °C and it was diluted with ethyl acetate (500 mL). The organic layer washed with water (2X100 mL) and dried over sodium sulphate and it was evaporated under reduced pressure to obtain crude product. The crude product was further purified by column chromatography to give 4-Ethynyl-benzaldehyde as a light yellow solid (1.8 g, 72 percent)
72%
Stage #1: With potassium carbonate In methanol at 25℃; for 1 h; Stage #2: With water In methanol; ethyl acetate
To a solution of 4-Trimethylsilanylethynyl-benzaldehyde (4.0 g, 19.7 mmol) in methanol (50 mL) was added K2CO3 (275 mg, 1.97 mmol) at 25° C. The reaction mixture stirred at same temperature over a period of 60 min. Methanol was evaporated to the half volume at 35° C. and it was diluted with ethyl acetate (500 mL). The organic layer washed with water (2*100 mL) and dried over sodium sulphate and it was evaporated under reduced pressure to obtain crude product. The crude product was further purified by column chromatography to give 4-Ethynyl-benzaldehyde as a light yellow solid (1.8 g, 72percent).
71%
With potassium carbonate In methanol at 20℃;
To a solution of 4-((trimethylsilyl)ethynyl)benzaldehyde (1.63 g, 8.06 mmol) in CH3OH (15 mL) was added K2CO3 (112 mg, 0.810 mmol). The reaction mixture was stirred at room temperature overnight and concentrated under reduced pressure. The residue was purified by flash column chromatography (silica gel, petroleum benzine ramping to petroleum benzine:EtOAc = 98:2) to give 10 as a pale yellow solid (750 mg, 71percent). RF (EtOAc:hexane = 1:5) 0.56. m.p. 9192 °C (lit. [7] m.p. 87 °C). IR νmax/cm-1 3223, 2837, 2739, 1695, 1601, 1561, 1388, 1294, 1207, 1165, 829. 1H NMR (400 MHz, CDCl3) δ 3.31 (s, 1H, C≡CH), 7.63 (d, 2H, J 8.0, Ph-H), 7.84 (d, 2H, J 8.0, Ph-H), 10.0 (s, 1H, CHO). 13C NMR (100 MHz, CDCl3) δ 81.2, 82.7, 128.4, 129.6, 132.8, 136.1, 191.5 (two carbon signals overlapping or obscured). MS (GC-EI) 101.0 ([MCHO]+, 41percent), 129.0 (M+, 100percent). The spectroscopic data were in agreement with those in the literature [7].
0.29 g
With potassium carbonate In methanol at 20℃; for 1 h;
A mixture of 4-((trimethylsilyl)ethynyl)benzaldehyde 4 (1g, 4.94 mmol) and potassium carbonate (1g, 7.41 mmol) were stirred in methanol (25 mL) at room temperature for 1 hour. The reaction mixture was diluted with ethylacetate (20 mL) and washed with water (2 x 20 mL) followed by brine solution. The organic solvent was concentrated under reduced pressure to obtain compound 5. Yellow solid; Yield: 0.29 g (90percent); M.p.: 84-86°C;IR (KBr): Umax 3454, 329, 3220, 2836, 2784, 2739, 2098, 1930, 1699, 1686, 1601, 1560, 1408, 1386, 1364, 1303, 1286, 1206, 1163, 1102, 1012, 975, 954, 924, 844, 829, 739, 679, 581, 530, 508 cm-1;1H NMR (400 MHz, CDCl3): d3.30 (1 H, s), 7.66 (d, J = 8.20 Hz, 2H), 7.86 (d, J = 8.20 Hz, 2H), 10.02 (s, 1H).
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3
[ 1122-91-4 ]
[ 1066-54-2 ]
[ 77123-57-0 ]
Yield
Reaction Conditions
Operation in experiment
100%
With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); triethylamine In tetrahydrofuran at 20℃; Inert atmosphere
To a solution of 4-bromobenzaldehyde 7 (3.70 g, 20.0 mmol), CuI (380 mg, 2.00 mmol) and Pd(PPh3)4 (924 mg, 800 mol) in THF (60 mL) were added Et3N (11.2 mL, 80.3 mmol) and trimethylsilylacetylene (4.24 mL, 30.0 mmol). The reaction mixture was stirred at room temperature under Ar overnight and filtered, and the solids were washed with EtOAc (30 mL). The filtrate and EtOAc washing were combined and concentrated under reduced pressure, and the residue was purified by flash column chromatography (silica gel, petroleum benzine ramping to petroleum benzine:EtOAc = 98:2) to give 4-((trimethylsilyl)ethynyl)benzaldehyde as a pale brown solid (4.04 g, 100percent). RF (petroleum benzine:EtOAc = 4:1) 0.87. m.p. 6667 °C (lit. [7] m.p. 70 °C). IR νmax/cm-1 2960, 2899, 2832, 2733, 2159, 1702, 1600, 1563, 1412, 1384, 1303, 1251, 1205, 1165, 862, 842. 1H NMR (300 MHz, CDCl3) δ 0.19 (s, 9H, Si(CH3)3), 7.47 (d, 2H, J 8.1, Ph-H), 7.68 (d, 2H, J 7.8, Ph-H), 9.87 (s, 1H, CHO). 13C NMR(75 MHz, CDCl3) δ 0.3, 98.8, 103.8, 129.1, 129.3, 132.3, 135.5, 191.0 (four carbon signals overlapping or obscured). MS (GC-EI) 187.1 ([MCH3]+, 100percent), 202.0 (M+, 8percent). The spectroscopic data were in agreement with those in the literature. [7]
100%
Stage #1: for 0.0833333 h; Sealed tube; Sonication Stage #2: for 3 h; Sealed tube
General procedure: In a tightly sealed tube (septa system),aryl halides (5.5 mmol) and 5percent nanocatalyst Pd/Cu, PPh3 (17 mg) were suspended in drytriethylamine (10 mL). The mixture was placed in an ultrasound bath and sonicated for 5 min.Then, the acetylene compound (5.6 mmol) was added and the mixture was stirred for 3 h. Themixture was cooled to room temperature and the catalyst was centrifuged, filtered and washedwith ethyl acetate (3 x 10 mL). The filtrate was washed three times with deionized water (3 x 15mL) and then dried over magnesium sulfate, filtered and concentrated under reduced pressureto give the product.
99%
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In tetrahydrofuran at 40℃; for 2 h;
p-bromobenzaldehyde (1.85 g, 10 mmol) was dissolved in 15 mL of anhydrous THF and trimethylsilylacetylene was added.(1.47 g, 15 mmol), bistriphenylphosphine dichloropalladium (70 mg, 0.1 mmol), cuprous iodide (38 mg, 0.2 mmol), and 5 ml triethylamine.Reaction at 40 °C for 2 h. Spin-dry the THF, and column-purify with PE and DCM (2:1 by volume) to obtain 2.0 g of compound 4 as a white solid. The yield is 99percent.
98.6%
for 2 h; Heating / reflux
Example 4Part A: Synthesis of 4- [(TrimethylsilyDethynyll benzaldehydeA deaerated solution of 24.5 g (132 mmol) of 4-bromobenzaldehyde and 1.00 g of triphenylphosphine in 300 ml of anhydrous triethylamine was treated with 20.0 g (204 mmol) of ethynyltrimethylsilane and then 0.3 g of palladium(II)acetate under argon. The mixture was heated at reflux for 2 h, cooled and filtered to give 24.Og (100 percent) of triethylamine hydrobromide. The filtrate was concentrated to an oil which solidified into long needles. The crude material was dissolved in hexane and filtered through silica gel to give 26.3 g (130 mmol, 98.6 percent) of 4-[(trimethylsilyl)ethynyl]benzaldehyde. The material was used in the next step without any further purification. 1H-NMR (CDCl3, 400 MHz): δ[ppm] = 0.21(s, 9 H), 7.60 (q, 4 H, J = 7.0 Hz), 9.85 (s, 1 H)
96.1%
With triphenylphosphine In triethylamine for 2 h; Heating / reflux
To a solution of 4-bromobenzaldehyde (10.00 g, 54.08 mmol) and triphenylphosphine (0.500 g, 1.91 mmol) in anhydrous triethylamine (80 mL) under Angon, were added ethynyltrimethylsilane (6.00 g, 61.09 mmol) and palladium (II) acetate (0.100 g, 0.445 mmol). The final mixture was heated to reflux for 2 hours, and then it was cooled down to room temperature and filtrated. The filtrate was concentrated under vacuum to a thick oil, which was purified by column chromatography (dichloromethane/petroleum ether 1:4) and recrystallized from cold cyclohexane to give 10.5 g (96.1percent yield) of 4-(trimethylsilylethynyl)benzaldehyde; MS m/e 187.2 (M+); 1H-NMR (CDCl3) ? ppm: 0.27 (s, 9H, SiMe3), 7.60 (d, 2H, ArH, J=8.1 Hz), 7.82 (d, 2H, ArH, J=8.1 Hz), 10.00 (s, 1H, CHO)].
96%
With copper(l) iodide; triethylamine; triphenylphosphine; palladium dichloride In tetrahydrofuran for 2 h; Reflux
To a stirred mixture of 3 (4.61 g, 24.9 mmol), CuI (193 mg,1.01 mmol, 0.041 equiv.), PdCl2 (93 mg, 0.52 mmol, 0.021 equiv.),and PPh3 (405 mg, 1.54 mmol, 0.062 equiv.) in 25 mL of THF was addedEt3N (5.2 mL, 37.3 mmol, 1.5 equiv.)and trimethylsilylacetylene(6 mL, 42.5 mmol, 1.7 equiv.). The mixture was stirred for 2 hours at refluxtemperature, then poured into water and extracted with CHCl3. TheCHCl3 layer was washed with brine, dried over Na2SO4,and filtered. The filtrate was evaporated, and silica gel flash column chromatography(n-hexane to n-hexane/AcOEt = 20/1) of the residue gave 4.82 g (96percent) of 4 as a brown solid: 1H NMR(CDCl3 500 MHz, δ; ppm) 10.00 (1H, s), 7.82 (2H, dd, J = 6.7 Hz, 1.8 Hz), 7.61 (2H, d, J = 8.2 Hz), 0.27 (9H, s).
92%
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In tetrahydrofuran at 40℃; Inert atmosphere
Trimethylsilylacetylene (5mL, 4.03g, 41.0mmol) was added to a solution of 4-bromobenzaldehyde (5.00g, 27.0mmol), Pd(PPh3)2Cl2 (50mg, 0.07mmol), and CuI (25mg, 0.13mmol) in distilled THF (40mL) under argon. Then, triethylamine (6.5mL) was added and the reaction mixture was heated at 40°C overnight. The solvent was evaporated under reduced pressure. The obtained residue was extracted in DCM, washed in water, dried with MgSO4, and then taken into dryness. The solid was then purified by column chromatography on silica gel using a mixture of heptane/DCM (1:1) as eluent. The compound 9 was obtained as a pale yellow solid to yield 5.04g (92percent). 1H NMR (400MHz, CDCl3, δ in ppm): 10.01 (s, 1H, CHO), 7.83 (d, 2H, Hphenyl, 3JHH=7.6Hz), 7.62 (d, 2H, Hphenyl, 3JHH=7.2Hz), 0.29 (s, 9H, (CH3)3Si).
89%
for 6 h; Reflux
A deaerated solution of 4-bromobenzaldehyde (3, 4.87 g, 25 mmol),triphenylphosphine (0.33 g, 1.25 mmol), PdCl2 (45 mg, 0.25 mmol), and Cu(OAc)2 (48 mg, 0.25 mmol) inanhydrous triethylamine (60 mL) was treated with trimethylsilylacetylene (5.5 mL, 38 mmol). The mixture wasbrought to reflux for 6 h. After cooling, the precipitated triethylamine hydrobromide was filtered off, and thesolvent was evaporated. The crude material was purified by silica gel column chromatography (silica gel 120 g,hexanes/ethyl acetate = 90/10), affording 4-((trimethylsilyl)ethynyl)benzaldehyde (4.49 g, 89percent yield) as a yellowsolid. 4-((Trimethylsilyl)ethynyl)benzaldehyde (4.05 g, 20 mmol) was treated with K2CO3 (2.28 mg, 2 mol) inMeOH (24 mL) at room temperature for 24 h. The solvent was removed in vacuo. The crude material was purifiedby silica gel column chromatography (silica gel 120 g, hexanes/ethyl acetate = 90/10), affording 4-ethynylbenzaldehyde (5; 2.20 g, 85percent yield) as a yellow solid.
88%
With copper(l) iodide; N-cyclohexyl-cyclohexanamine In tetrahydrofuran at 30℃; for 17 h;
[Example A-18] Synthesis of 4-[(trimethylsilyl)ethynyl]benzaldehyde from 4-bromobenzaldehyde and trimethylsilylacetylene (Synthesis in which tri-tert-butylphosphonium tetraphenylborate was handled in air) A 50-ml four-necked flask was equipped with a stirrer, a thermometer and a reflux condenser. 0.034 g (0.15 mmol) of palladium (II) acetate, 0.019 g (0.1 mmol) of copper (I) iodide, 1.088 g (6 mmol) of dicyclohexylamine and 9 ml of tetrahydrofuran were weighed in the flask, followed by stirring. Further, 0.157 g (0.3 mmol) of tri-tert-butylphosphonium tetraphenylborate obtained in Example A-1 was weighed in air and added into the flask. The flask was purged with argon, followed by stirring at 30°C for 30 minutes. 0.925 g (5 mmol) of 4-bromobenzaldehyde and 0.589 g (6 mmol) of trimethylsilylacetylene were added, followed by stirring at 30°C for 17 hours. After the completion of the reaction, 10 ml of tetrahydrofuran, 5 ml of toluene and 15 ml of saturated sodium chloride solution were added, followed by separation. The organic phase was purified by column chromatography to afford 0.893 g of 4-[(trimethylsilyl)ethynyl]benzaldehyde (yield: 88 molpercent based on 4-bromobenzaldehyde). The identification of the product was made by 1H-NMR and 13C-NMR. (1) 1H-NMR spectrum (δ in CDCl3) 0.26 ppm (s, 9H, H3C) 7.59 ppm (d, J=8.1 Hz, 2H, ring proton) 7.81 ppm (d, J=8.1 Hz, 2H, ring proton) 9.99 ppm (s, 1H, HC) (2) 13C-NMR spectrum (δ in CDCl3) -0.2, 99.0, 103.8, 129.3, 129.4, 132.5, 135.6, 191.4 ppm
88%
With copper(l) iodide; N-cyclohexyl-cyclohexanamine In tetrahydrofuran at 30℃; for 17 h; In argon atmosphere
[Comparative Example 33] Synthesis of 4-[(trimethylsilyl)ethynyl]benzaldehyde from 4-bromobenzaldehyde and trimethylsilylacetylene (Synthesis in which tri-tert-butylphosphine was handled in argon) The procedures in Example A-18 or B-36 were repeated except that 0.157 g (0.3 mmol) of tri-tert-butylphosphonium tetraphenylborate of Example A-18 or 0.174 g (0.3 mmol) of tri-tert-butylphosphonium tetra-para-tolylborate of Example B-36 was replaced with 0.061 g (0.3 mmol) of tri-tert-butylphosphine, and except that the procedures were carried out in a glove box in which an argon atmosphere was strictly maintained. Consequently, 0.894 g of 4-[(trimethylsilyl)ethynyl]benzaldehyde was obtained (yield: 88 molpercent based on 4-bromobenzaldehyde). The identification of the product was made by 1H-NMR and 13C-NMR, and the results were in agreement with those of Example A-18 or B-36.
88%
With copper(l) iodide; N-cyclohexyl-cyclohexanamine In tetrahydrofuran at 30℃; for 17 h;
[Example B-36] [Similar to Example A-18] Synthesis of 4-[(trimethylsilyl)ethynyl]benzaldehyde from 4-bromobenzaldehyde and trimethylsilylacetylene (Synthesis in which tri-tert-butylphosphonium tetra-para-tolylborate was handled in air) A 50-ml four-necked flask was equipped with a stirrer, a thermometer and a reflux condenser. 0.034 g (0.15 mmol) of palladium (II) acetate, 0.019 g (0.1 mmol) of copper (I) iodide, 1.088 g (6 mmol) of dicyclohexylamine and 9 ml of tetrahydrofuran were weighed in the flask, followed by stirring. Further, 0.174 g (0.3 mmol) of tri-tert-butylphosphonium tetra-para-tolylborate obtained in Example B-3 was weighed in air and added into the flask. The flask was purged with argon, followed by stirring at 30°C for 30 minutes. 0.925 g (5 mmol) of 4-bromobenzaldehyde and 0.589 g (6 mmol) of trimethylsilylacetylene were added, followed by stirring at 30°C for 17 hours. After the completion of the reaction, 10 ml of tetrahydrofuran, 5 ml of toluene and 15 ml of saturated sodium chloride solution were added, followed by separation. The organic phase was purified by column chromatography to afford 0.890 g of 4-[(trimethylsilyl)ethynyl]benzaldehyde (yield: 88 molpercent based on 4-bromobenzaldehyde). The identification of the product was made by 1H-NMR and 13C-NMR. (1) 1H-NMR spectrum (δ in CDCl3) 0.26 ppm (s, 9H, H3C) 7.59 ppm (d, J=8.1 Hz, 2H, ring proton) 7.81 ppm (d, J=8.1 Hz, 2H, ring proton) 9.99 ppm (s, 1H, HC) (2) 13C-NMR spectrum (δ in CDCl3) -0.2, 99.0, 103.8, 129.3, 129.4, 132.5, 135.6, 191.4 ppm
85%
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In tetrahydrofuran at 20℃; for 24 h;
To a mixture of PdCl2(PPh3)2 (175 mg, 0.3 mmol) andCuI (190 mg, 1.0 mmol) in THF (30 mL), 4-bromobenzaldehyde (1.85 g, 10 mmol), trimethylsilyl acetylene(1.12 mL, 12 mmol), and NEt3 (10 mL) were added.The resulted mixture was stirred for 24 h at room temperature.The solvent was removed and 30 mL CH2Cl2 wasadded. The mixture was washed with water (3 30 mL). Theorganic phase was dried with MgSO4 and the solvent wasremoved by rotary evaporation. Purification by columnchromatography (Silica gel, CH2Cl2/hexane 1:2) gave 4-(2-(trimethylsilyl)ethynyl) -benzaldehyde derivative as whitesolid (yield 85percent).To a stirred solution of 4-(2-(trimethylsilyl)ethynyl) benzaldehyde(5 mmol) in CH3OH (30 mL), K2CO3 (69 mg, 0.5mmol) was added. The mixture was stirred for 24 h at roomtemperature, and the solvent was removed. The residue wasdiluted with 30 mL Et2O and washed with water (3 30mL). The organic phase was dried over MgSO4 and the solventwas removed by rotary evaporation. Purification by aflash colum chromatography (Silica gel, Et2O) provide 5 aswhite solid (546 mg, yield 84percent).1H NMR (400 MHz, CDCl3)
81%
With triethylamine In tetrahydrofuran at 25 - 30℃; for 3 - 20.5 h;
Example 1; Synthesis of 4-trimethylsilanylethynyl-benzaldehyde (2); 4-Bromobenzaldehyde (1) (185 g, 1.0 mole) was dissolved in THF (1 L) followed by addition of copper (I) iodide (7.6 g, 0.04 mol), dicholobis(triphenylphospine) palladium (II) (14.02 g, 0.02 mol) and triethylamine (151.5 g, 1.5 mol). Ethynyltrimethylsilane (109.1 g, 1.11 mol) was added from addition funnel as a solution in THF (0.2 L). The reaction was stirred at 30° C. for 30 min and then at 25° C. for 20 hours. Analysis by HPLC indicated the completion of the reaction. THF was removed and the residue was treated with hexane (1.8 L). The solid was removed by filtration and the filter cake washed with hexane (0.3 L). The combined hexane solution was washed with water (2.x.0.5 L). Hexane was removed in a rotovap. The residue was dissolved in EtOH (0.5 L) at 50° C. The solution was then slowly cooled to 16° C. and was stirred for 30 minutes. Product started to crystallize. The mixture was further cooled to 5° C. 1:1 of EtOH/H2O (0.24 L) was added slowly. The mixture was stirred at 5° C. for 30 minutes. Solid was collected by filtration, washed with 4:1 of EtOH/H2O (0.2 L) and dried to provide 137.0 g of product. The mother liquor was concentrated to dryness. The residue was partitioned between hexane (0.5 L) and brine (0.25 L). Hexane layer was separated and concentrated to dryness. The residue was crystallized from hexane (40 ml) and further recrystallized from 4:1 of EtOH/H2O (0.1 L) to provide second crop of aldehyde 2 (27.0 g). The combined yield for aldehyde 2 was 81percent. 1H NMR (300 MHz, CDCl3) δ 0.081(s, 9H), 7.41(d, 2H, J=8.1 Hz), 7.63(d, 2H, J=8.4 Hz), 9.81 (s, 1H).
80%
at 20℃; Inert atmosphere; sealed tube; Reflux
B. 4-ethynylbenzaldehyde; A degassed solution of 4-bromobezaldehyde (6.0 g, 32.4 mmol) and triphenylphosphine (0.17 g, 0.65 mmol) in 60 mL of anhydrous triethylamine was added ethynyltrimethylsilane (26.7 mL, 48.6 mmol) followed by palladium (II) acetate (0.072 g, 0.32 mmol) at room temperature under argon atmosphere. The reaction mixture was heated at reflux for 2 h in sealed tube. The reaction mass was cooled to room temperature and the precipitated solid was filtered. The filtrate was concentrated to provide crude compound. The crude compound was purified by column chromatography (silica gel, 100-200 mesh) by using 1percent ethyl acetate in pet-ether as mobile phase to provide 4- ((trimethylsilyl)ethynyl)benzaldehyde (5.2 g, 80percent). This compound was taken up in methanol (100 mL), to which potassium carbonate (0.341 g, 2.47 mmol) was added at room temperature. The reaction mass was stirred for 2 h. The solvent was removed under reduced pressure and the residue was diluted with dichloromethane (50 mL). The organic solution was washed with water (50 mL), brine solution (25 mL), dried over anhydrous magnesium sulfate and evaporated under reduced pressure to get 4-ethynylbenzaldehyde as light brown solid (3.0 g, 94percent).LC-MS: [M+H]+ 131.2 Mass: calculated for C9H6O, 130.15IH NMR (400 MHz, δ ppm, CDC13): δ 10.02 (s, IH), 7.85 (d, 2H), 7.65 (d, 2H), 3.29 (s, IH)
80%
Reflux
To a solution of 4-bromobenzaldehyde (10.0 g, 54.04 mmol) in diisopropylamine (600 mL) were added bistriphenylphosphine palladium (II) chloride (380 mg, 0.54 mmol) and Cul (205 mg, 1.08 mmol). The reaction mixture was degassed for 20 min. Then the reaction mixture was cooled to ice temperature and trimethyl silylacetalide (11.2 mL, 81.06 mmol) was added drop wise at same temperature for 30 min and it was refluxed over a period of 3 h. Diisopropylamine was evaporated under reduced pressure and the residue was diluted with ethyl acetate (1000 mL). The ethyl acetate layer was washed with IN Hydrochloric acid (2X100 mL), saturated sodium bicarbonate (1X100 mL) and water (2X 200 mL). Organic layer was dried over sodium sulphate and it was evaporated under reduced pressure to obtain crude product. The crude product was further purified by column chromatography to give 4-Trimethylsilanylethynyl-benzaldehyde as a colorless solid (8.5 g, 80 percent).
80%
at 0℃; for 3.5 h; Reflux
To a solution of 4-bromobenzaldehyde (10.0 g, 54.04 mmol) in diisopropylamine (600 mL) were added bistriphenylphosphine palladium (II) chloride (380 mg, 0.54 mmol) and CuI (205 mg, 1.08 mmol). The reaction mixture was degassed for 20 min. Then the reaction mixture was cooled to ice temperature and trimethyl silylacetalide (11.2 mL, 81.06 mmol) was added drop wise at same temperature for 30 min and it was refluxed over a period of 3 h. Diisopropylamine was evaporated under reduced pressure and the residue was diluted with ethyl acetate (1000 mL). The ethyl acetate layer was washed with 1N Hydrochloric acid (2*100 mL), saturated sodium bicarbonate (1*100 mL) and water (2*200 mL). Organic layer was dried over sodium sulphate and it was evaporated under reduced pressure to obtain crude product. The crude product was further purified by column chromatography to give 4-Trimethylsilanylethynyl-benzaldehyde as a colorless solid (8.5 g, 80percent).
74%
at 40℃;
Trimethylsilylacetylene (19.4 mL, 135.9 mmol) was added to a mixture of 4-bromobenzaldehyde (5.0 g, 27.18 mmol), Pd(PPh3)2Cl2 (950 mg, 1.36 mmol) and CuI (520 mg, 2.72 mmol) in Et3N (60 mL). The mixture was stirred overnight at 40 °C. After cooling to room temperature, the resulting ammonium salt was filtered off, and the solvent was removed by rotary evaporation. The residue was purified by silica gel column chromatography with petroleum ether as eluent to afford 4-((trimethylsilyl)ethynyl)benzaldehyde as a yellow powder after removal of the solvent (4.0 g, 74percent). 1H NMR (300 MHz, CDCl3) δ 10.00 (s, 1H), 7.82 (d, J = 8.5 Hz, 2H), 7.60 (d, J = 8.2 Hz, 2H), 0.27 (s, 9H).
70%
at 0 - 20℃; for 3.5 h; Reflux
A solution of 548 4-bromobenzaldehyde (10 g, 54.64 mmol) in 549 diisopropyl amine (500 mL) was charged with 550 bis(triphenylphosphine)palladium(II) dichloride (380 mg, 0.546 mmol) and 314 copper iodide (205 mg, 1.09 mmol) and degassed for 20 min. The reaction mixture was cooled to 0° C. and followed by dropwise addition of 551 trimethyl silyl acetylene (11.2 mL, 81.06 mmol) for a period of 30 min. The reaction mixture was allowed to attain room temperature and further refluxed for 3 h. The reaction mixture was cooled to room temperature and HBr salt formed was filtered. The filtrate was concentrated in vacuo, diluted with ethyl acetate and washed with 1N HCl solution followed by saturated 125 sodium bicarbonate and water. The separated organic layers were dried over anhydrous Na2SO4, filtered and concentrated in vacuo resulting in the crude 545 compound which was purified by column chromatography on silica gel eluting with 0-5percent ethyl acetate in n-hexane to afford 7.7 g, 70percent yield, of the title compound as an off white solid. 1H NMR (400 MHz, CDCl3) δ=10.00 (s, 1H), 7.82 (d, J=8.31 Hz, 2H), 7.60 (d, J=7.83 Hz, 2H), 0.27 (s, 9H); MS (ES+): m/z=244.16 [M+H]+; LCMS: tR=3.58 min.
1.2 g
With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); triethylamine In tetrahydrofuran at 18 - 25℃; Inert atmosphere
A suspension of 4-bromobenzaldehyde (1 g, 5mmol), Pd(PPh3 ) 4 (0.23 g, 0.2 mmol). Cui (95 mg, 0.5mmol), triethylamine (2.02 g, 20 mmol) and ethynyltrimethylsilane(0.79 g, 8 mmol) in THF (20 mL) under a N2atmosphere was stirred at RT overnight. The mixture wasfiltered and the filtrate was concentrated. The residue waspurified by silica-gel colunm chromatography to give 1.2 gof 4-((trimethylsilyl)ethynyl)benzaldehyde as a light brownsolid.
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4
[ 15164-44-0 ]
[ 1066-54-2 ]
[ 77123-57-0 ]
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5
[ 3375-31-3 ]
[ 1122-91-4 ]
[ 1066-54-2 ]
[ 77123-57-0 ]
Yield
Reaction Conditions
Operation in experiment
96.1%
With triphenylphosphine In triethylamine
4-Ethynylbenzaldehyde (13): To a solution of 4-bromobenzaldehyde (10.00 g, 54.08 mmol) and triphenylphosphine (0.500 g, 1.91 mmol) in anhydrous triethylamine (80 mL) under argon were added ethynyltrimethylsilane (6.00 g, 61.09 mmol) and palladium (II) acetate (0.100 g, 0.445 mmol). The final mixture was heated to reflux for 2 hours, and was then cooled to room temperature and filtered. The filtrate was concentrated under vacuum to a thick oil, which was purified by column chromatography (dichloromethane/petroleum ether 1:4) and recrystallized from cold cyclohexane to give 10.5 g (96.1percent yield) of 4-(trimethylsilylethynyl)benzaldehyde [MS m/e 187.2 (M+); 1H-NMR (CDCl3) δ ppm: 0.27 (s, 9H, SiMe3), 7.60 (d, 2H, ArH, J=8.1 Hz), 7.82 (d, 2H, ArH, J=8.1 Hz), 10.00 (s, 1H, CHO)].
96.1%
With triphenylphosphine In triethylamine
4-Ethynylbenzaldehyde (13): To a solution of 4-bromobenzaldehyde (10.00 g, 54.08 mmol) and triphenylphosphine (0.500 g, 1.91 mmol) in anhydrous triethylamine (80 mL) under argon were added ethynyltrimethylsilane (6.00 g, 61.09 mmol) and palladium (II) acetate (0.100 g, 0.445 mmol). The final mixture was heated to reflux for 2 hours, and was then cooled to room temperature and filtered. The filtrate was concentrated under vacuum to a thick oil, which was purified by column chromatography (dichloromethane/petroleum ether 1:4) and recrystallized from cold cyclohexane to give 10.5 g (96.1percent yield) of 4-(trimethylsilylethynyl)benzaldehyde [MS m/e 187.2 (M+); 1H-NMR (CDCl3) δ ppm: 0.27 (s, 9H, SiMe3), 7.60 (d, 2H, ArH, J=8.1 Hz), 7.82 (d, 2H, ArH, J=8.1 Hz), 10.00 (s, 1H, CHO)].
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7
[ 275386-60-2 ]
[ 77123-57-0 ]
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8
[ 624-38-4 ]
[ 77123-57-0 ]
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9
[ 68-12-2 ]
[ 77123-57-0 ]
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10
[ 106-37-6 ]
[ 77123-57-0 ]
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11
[ 77123-57-0 ]
[ 275386-60-2 ]
Yield
Reaction Conditions
Operation in experiment
94%
Stage #1: With sodium tetrahydroborate In ethanol at 20℃; Stage #2: With water; ammonium chloride In ethanol
Part B: Synthesis of 4- [(TrimethylsilvDethynyl-phenyll methanolTo a stirred solution of 4-[(trimethylsilyl)ethynyl]benzaldehyde (0.50 g, 2.47 mmol) in dry ethanol (10 ml) was added sodium borohydride (0.32 g, 8.50 mmol). The reduction was almost instantaneous at room temperature. The reaction mixture was carefully quenched with half-saturated aqueous ammonium chloride solution (30 ml) and extracted with dichloromethane (2 x 20 ml). The combined organic layers were washed with saturated <n="66"/>brine (2 x 15 ml), dried over MgSO4, filtered and concentrated under reduced pressure to yield 4-[(trimethylsilyl)ethynyl-phenyl]methanol (0.47 g, 2.32 mmol, 94percent). The material was used in the next step without any further purification.1H-NMR (CDCl3, 200 MHz): δ[ppm] = 0.25 (s, 9H), 1.65 (t, IH, J = 5.9 Hz), 4.69 (d, 2H5 J = 5.8 Hz), 7.29 (d, 2H, J = 8.3 Hz), 7.46 (d, 2H, J = 8.3 Hz)
With copper(l) iodide; triethylamine In N,N-dimethyl-formamide at 50℃; for 6h;
88%
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; triphenylphosphine In tetrahydrofuran at 20 - 65℃; for 26h; Inert atmosphere; Green chemistry;
87%
With diethylamine Ambient temperature;
86%
With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); triethylamine In tetrahydrofuran at 23℃; for 16h; Inert atmosphere;
85%
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine at 20℃; for 2h;
73%
With N-ethyl-N,N-diisopropylamine In tetrahydrofuran for 24h;
73%
With copper(l) iodide; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 20℃; for 24h;
73%
With copper(l) iodide; triethylamine In tetrahydrofuran
64%
With triphenyl-arsane; TEA at 35℃; for 12h;
53%
With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); diethylamine In N,N-dimethyl-formamide at 120℃; Inert atmosphere;
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In tetrahydrofuran
Stage #1: p-(iodophenyl)carboxaldehyde; trimethylsilylacetylene With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triphenylphosphine In tetrahydrofuran Sealed tube; Inert atmosphere;
Stage #2: With triethylamine In tetrahydrofuran at 65℃; Sealed tube; Inert atmosphere;
4-(2-(trimethylsilyl)ethynyl)benzaldehyde 4
To a solution of 4-iodobenzaldehyde 3 (1g, 4.30 mmol) in tetrahydrofuran (12 mL), in a seal tube, were added sequentially, copper(I) iodide (0.14 mmol), triphenylphosphine (0.39 mmol), bis(triphenylphosphine)palladium(II) dichloride (0.14 mmol) and trimethylsilylacetylene (0.59 mL, 4.14 mmol) under argon atmosphere. After string for 15 min, triethylamine (12.9 mmol) was added and the resultant mixture was heated at 65C for 30 min. The reaction contents were diluted with ethyl acetate (15 mL), washed with water (2 X 15 mL), washed with brine solution (10 mL). The organic layer was separated and dried over Na2SO4. The solvent was evaporated under reduced pressure to obtain compound 4 as a viscous pale yellow oily liquid. The crude compound was utilized in the next step without further purification.
Stage #1: p-(iodophenyl)carboxaldehyde With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine at 20℃; for 0.5h; Schlenk technique; Inert atmosphere;
Stage #2: trimethylsilylacetylene at 20℃; for 4h; Schlenk technique; Inert atmosphere;
Part B: Synthesis of 4- [(TrimethylsilvDethynyl-phenyll methanolTo a stirred solution of 4-[(trimethylsilyl)ethynyl]benzaldehyde (0.50 g, 2.47 mmol) in dry ethanol (10 ml) was added sodium borohydride (0.32 g, 8.50 mmol). The reduction was almost instantaneous at room temperature. The reaction mixture was carefully quenched with half-saturated aqueous ammonium chloride solution (30 ml) and extracted with dichloromethane (2 x 20 ml). The combined organic layers were washed with saturated <n="66"/>brine (2 x 15 ml), dried over MgSO4, filtered and concentrated under reduced pressure to yield 4-[(trimethylsilyl)ethynyl-phenyl]methanol (0.47 g, 2.32 mmol, 94%). The material was used in the next step without any further purification.1H-NMR (CDCl3, 200 MHz): delta[ppm] = 0.25 (s, 9H), 1.65 (t, IH, J = 5.9 Hz), 4.69 (d, 2H5 J = 5.8 Hz), 7.29 (d, 2H, J = 8.3 Hz), 7.46 (d, 2H, J = 8.3 Hz)
Stage #1: 4-[(trimethylsilyl)ethynyl]bezaldehyde With tetrabutyl ammonium fluoride In tetrahydrofuran; water Inert atmosphere;
Stage #2: With chloro-trimethyl-silane In tetrahydrofuran; water for 0.25h; Inert atmosphere;
Stage #3: With N,N,N,N,-tetramethylethylenediamine; oxygen; copper(l) chloride In tetrahydrofuran; water Inert atmosphere;
General Procedure O: Synthesis of compounds in Table O; Compounds in Table O were produced as part of a one dimensional array with the only variant being the aldehyde monomer which is given in Table O. The amines were purchased pre- weighed from the Sigma Aldrich Custom Packaged Reagent service.; In a 20 mL vial a solution of 4-(trimethylsilyl)ethynylbenzaldehyde (1.2 eq) dissolved in MeOH:DCM (1.5 mL) was added, followed by the addition of amine core (20 mg, leq.) dissolved in MeOH:DCM (1.0 mL), and HOAc (3 eq.). The mixture was shaken at about 50 C for about 2 h and MP-cyanoborohydride resin (5 eq.) (Biotage) was added. This reaction mixture was allowed to stir overnight at about 50 C. The reaction was checked by LC/MS and concentrated to dryness. The residue was dissolved in 1 : 1 DMSO/MeOH and purified by reverse phase HPLC. Product was characterized by MS and LC/MS (Table 2, Method a).
Stage #1: 2,4-dimethyl-1H-pyrrole; 4-[(trimethylsilyl)ethynyl]bezaldehyde In tetrahydrofuran at 20℃; for 0.5h; Inert atmosphere;
Stage #2: With trifluoroacetic acid In tetrahydrofuran at 20℃; for 12h; Inert atmosphere;
Stage #3: boron trifluoride diethyl etherate Further stages;
a Step a
3.0 mmol of 4-trimethylsilylacetylbenzaldehyde 1-1 and 7.6 mmol2,4-Dimethylpyrrole 2-1 was dissolved in 90 mL of anhydrous tetrahydrofuran (THF).Stir at room temperature and vigorously pass argon for 30 min,To remove the air inside the system.Then quickly add 2 drops of trifluoroacetic acid,The reaction mixture was further stirred in the presence of argon for 12 h at room temperature.Until the TLC plate showed that 4-trimethylsilylacetylbenzaldehyde disappeared.Dissolve 1 equivalent of DDQ in 10 mL of THF.Then, it was slowly added dropwise to the above reaction mixture.After stirring for 4 h, the reaction solution was transferred to an ice bath. 18 mL of Et3N was slowly added using a constant pressure dropping funnel, and after stirring for 5 min, 19 mL of BF3.OEt2 was slowly added. After stirring at room temperature for 12 h, the reaction was stopped.After the reaction solution was repeatedly extracted three times with dichloromethane and water,It was dried over anhydrous sodium sulfate overnight. After spinning the solvent,Separated by column chromatography using dichloromethane and petroleum ether 1:2 as the eluent.0.82 g of orange-yellow solid product 3-1 was isolated, yield 65%
65%
Stage #1: 2,4-dimethyl-1H-pyrrole; 4-[(trimethylsilyl)ethynyl]bezaldehyde In tetrahydrofuran at 20℃; for 0.5h; Inert atmosphere;
Stage #2: With trifluoroacetic acid In tetrahydrofuran at 20℃; for 12h; Inert atmosphere;
Stage #3: boron trifluoride diethyl etherate Further stages;
23%
Stage #1: 2,4-dimethyl-1H-pyrrole; 4-[(trimethylsilyl)ethynyl]bezaldehyde With trifluoroacetic acid In dichloromethane at 20℃; for 6h; Inert atmosphere;
Stage #2: With 2,3-dicyano-5,6-dichloro-p-benzoquinone In dichloromethane for 1h;
Stage #3: boron trifluoride diethyl etherate With triethylamine In dichloromethane
With tetrakis(acetonitrile)copper(I)tetrafluoroborate; 1-(tert-butoxycarbonyl)-L-proline; tris-(o-tolyl)phosphine In dichloromethane at 3 - 5℃; for 168h; Molecular sieve; Inert atmosphere;
With tetrakis(acetonitrile)copper(I)tetrafluoroborate; 1-(tert-butoxycarbonyl)-L-proline; tris-(o-tolyl)phosphine In dichloromethane at 0 - 5℃; for 168h; Molecular sieve; Inert atmosphere;
With tetrakis(acetonitrile)copper(I)tetrafluoroborate; 1-(tert-butoxycarbonyl)-L-proline; tris-(o-tolyl)phosphine In dichloromethane at 0 - 5℃; for 168h; Molecular sieve; Inert atmosphere;
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