* 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 tetrabutyl ammonium fluoride In tetrahydrofuran at 0 - 20℃; for 3 h;
To a solution of (4-bromophenyl) methanol (935mg, 5mmol) in dry TEA was added Pd (PPh3) 2Cl2 (175mg, 0.25mmol) , CuI (48mg, 0.25mmol) and P (t-Bu) 3 (51mg, 0.25mmol) under N2 atmosphere. The reaction mixture was stirred for 5mins, followed by addition of ethynyltrimethylsilane (980mg, 10mmol) dropwise. The reaction mixture was then microwaved at 130 for 4hrs. The reaction mixture was cooled to room temperature, filtered over celite. Solvents were removed from the filtrate in vacuo, then the residue was extracted by EtOAc/H2O 3 times. The organic layer was combined, washed with brine, dried over Na2SO4 and further pufrified by silica gel column chromatography (PE/EA4/1) to give 670mg of (4- ( (trimethylsilyl) ethynyl) phenyl) methanol as a brown oil (66) .[0633]To a solution of (4- ( (trimethylsilyl) ethynyl) phenyl) methanol (250mg, 1.23mmol) in THF was added TBAF (500mg, 2.45mmol) in portions at 0. The reaction mixture was stirred at 0 to room temperature for 3hrs. Solvents were removed from the mixture in vacuo, and the residue was extracted by EtOAc/H2O 3 times. The organic layer was combined, washed with brine, dried over Na2SO4 and further pufrified by silica gel column chromatography (PE/EA4/1) to give 170mg of (4-ethynylphenyl) methanol as a brown oil (100) . 1H NMR (400Hz, CDCl3) δ7.45-7.49 (m, 2H) , 7.21-7.26 (m, 2H) , 4.69 (s, 1H) , 4.65 (s, 2H) .
100%
With potassium carbonate In methanol at 20℃; for 2 h;
Part C; Synthesis of (4-EthvnvI-phenyl)-methanoI4-[(Trimethylsilyl)ethynyl-phenyl]methanol (0.47 g, 2.30 mmol) was treated with potassium carbonate (0.34 g, 2.47 mmol) in 10 ml of methanol under argon at room temperature for 2 h. The solution was quenched with half saturated aqueous ammonium chloride solution (30 ml) and extracted with ether (2 x 25 ml). The combined organic layers were washed with saturated brine (2 x 20 ml), dried over MgSO4, filtered and concentrated under reduced pressure giving the product as a pale yellow oil in quantitative yield. The material was used in the next step without any further purification. IH-NMR (CDCl3, 200 MHz): δ[ppm] = 1.67 (tr, IH, J = 5.9 Hz), 4.71 (d, 2H, J = 5.9 Hz), 7.32 (d, 2H, J = 8.5 Hz), 7.50 (d, 2H, J = 8.5 Hz)
88%
With tetrabutyl ammonium fluoride In tetrahydrofuran
Example 4 Synthesis of (4-Ethynylphenyl)methanol (4) 3 (65 mg, 0.318 mmol) was dissolved in 1 ml of THF. TBAF (0.35 ml, 0.35 mmol) was added and the mixture was stirred at room temperature for 30 min. The solvent was removed under reduced pressure and the residue was purified by flash chromatography (AcOEt/Hexane 3:7) to afford 4 (37 mg, 0.28 mmol, 88percent yield) as a colorless solid.
87%
With tetrabutyl ammonium fluoride In tetrahydrofuran at 20℃; for 2 h;
To a solution of (4-((trimethylsilyl)ethynyl)phenyl)methanol (2.96 g, 14.47 mmol) in THF (29 mL) was added tetrabutylammonium fluoride solution (15.92 ml, 1M in THF). After addition, the reaction was stirred at ambient temperature for 2 h. All the volatile solvent was removed under reduced pressure, and the residue was dissolved in DCM (20 ml). Water (15 mL) was added, and the aqueous layer was extracted with DCM (15 mL X 2). The combined organic layer was washed with brine (30 mL), dried over Na2SO4, and filtered. The organic layer was concentrated under reduced pressure and the residue was purified by silica gel chromatography, by column chromatography with hexane/ethyl acetate (3/1, v/v) to obtain the compound 56 as a white solid (1.66 mg, 87percent yield): 1H NMR (400 MHz, CDCl3) _ 7.41 (d, J = 8.3 Hz, 2H), 7.17 (d, J = 8.6 Hz, 2H), 4.48 (s, 2H), 3.59 (s, 1H), 3.09 (s, 1H); 13C NMR (100 MHz, CDCl3) _ 141.5, 132.2, 126.7, 121.0, 83.5, 77.4, 64.3.
37 mg
With tetrabutyl ammonium fluoride In tetrahydrofuran at 20℃; for 0.5 h;
3 (65 mg, 0.318 mmol) was dissolved in 1 ml of THF. TBAF (0.35 ml, 0.35 mmol) was added and the mixture was stirred at room temperature for 30 min. The solvent was removed under reduced pressure and the residue was purified by flash chromatography (AcOEt/Hexane 3:7) to afford 4 (37 mg, 0.28 mmol, 88percent yield) as a colorless solid.
Reference：
[1] Angewandte Chemie - International Edition, 2004, vol. 43, # 29, p. 3814 - 3818
[2] Patent: WO2018/14802, 2018, A1, . Location in patent: Paragraph 0364
[3] Patent: WO2008/31157, 2008, A1, . Location in patent: Page/Page column 65
[4] Chemistry - A European Journal, 2013, vol. 19, # 29, p. 9452 - 9456
[5] Synthesis (Germany), 2014, vol. 46, # 3, p. 348 - 356
[6] Patent: US2013/266644, 2013, A1, . Location in patent: Page/Page column
[7] Patent: WO2018/160967, 2018, A1, . Location in patent: Page/Page column 87-88
[8] Chirality, 2015, vol. 27, # 8, p. 454 - 458
[9] Macromolecules, 2005, vol. 38, # 15, p. 6367 - 6373
[10] Tetrahedron Letters, 2000, vol. 41, # 17, p. 3123 - 3126
[11] Journal of the American Chemical Society, 2005, vol. 127, # 43, p. 15257 - 15264
[12] Journal of Medicinal Chemistry, 2010, vol. 53, # 2, p. 699 - 714
[13] Patent: CN105622638, 2016, A, . Location in patent: Paragraph 0328
[14] Patent: US9758545, 2017, B2, . Location in patent: Page/Page column 19; 20; 26; 27
3
[ 275386-60-2 ]
[ 63697-96-1 ]
Reference：
[1] Chemistry - A European Journal, 2013, vol. 19, # 29, p. 9452 - 9456
4
[ 275386-60-2 ]
[ 77123-57-0 ]
Reference：
[1] Chemical Communications, 2014, vol. 50, # 77, p. 11378 - 11381
5
[ 873-75-6 ]
[ 1066-54-2 ]
[ 275386-60-2 ]
Yield
Reaction Conditions
Operation in experiment
66%
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; tri-tert-butyl phosphine In triethylamine at 130℃; for 4 h; Inert atmosphere; Microwave irradiation
To a solution of (4-bromophenyl) methanol (935mg, 5mmol) in dry TEA was added Pd (PPh3) 2Cl2 (175mg, 0.25mmol) , CuI (48mg, 0.25mmol) and P (t-Bu) 3 (51mg, 0.25mmol) under N2 atmosphere. The reaction mixture was stirred for 5mins, followed by addition of ethynyltrimethylsilane (980mg, 10mmol) dropwise. The reaction mixture was then microwaved at 130 for 4hrs. The reaction mixture was cooled to room temperature, filtered over celite. Solvents were removed from the filtrate in vacuo, then the residue was extracted by EtOAc/H2O 3 times. The organic layer was combined, washed with brine, dried over Na2SO4 and further pufrified by silica gel column chromatography (PE/EA4/1) to give 670mg of (4- ( (trimethylsilyl) ethynyl) phenyl) methanol as a brown oil (66) .[0633]To a solution of (4- ( (trimethylsilyl) ethynyl) phenyl) methanol (250mg, 1.23mmol) in THF was added TBAF (500mg, 2.45mmol) in portions at 0. The reaction mixture was stirred at 0 to room temperature for 3hrs. Solvents were removed from the mixture in vacuo, and the residue was extracted by EtOAc/H2O 3 times. The organic layer was combined, washed with brine, dried over Na2SO4 and further pufrified by silica gel column chromatography (PE/EA4/1) to give 170mg of (4-ethynylphenyl) methanol as a brown oil (100) . 1H NMR (400Hz, CDCl3) δ7.45-7.49 (m, 2H) , 7.21-7.26 (m, 2H) , 4.69 (s, 1H) , 4.65 (s, 2H) .
1.274 g
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; diethylamine; triphenylphosphine In N,N-dimethyl-formamideMicrowave irradiation; Heating; Inert atmosphere
A solution of 4-Bromobenzyl alcohol (1.276 g, 6.82 mmol), Ethynyltrimethylsilane (1.061 ml, 7.51 mmol), PdCl2(PPh3)2 (24 mg, 0.034 mmol), Copper iodide (52 mg, 0.273 mmol), Triphenylphosphine (358 mg, 1.365 mmol), Diethylamine (10.70 ml, 102 mmol) in 2 ml of dry DMF (dimethylformamide) was heated under argon in a microwave oven at 150° C. for 30 min. The mixture was filtered. The filtrate was acidified with 1 M HCl and extracted 3 times with ether. The combined organic layers were washed with bicarbonate and water, dried over MgSO4 and concentrated to afford 3 (1.274 g, 6.23 mmol, 91percent yield) as a brown solid.
Reference：
[1] Chemistry - A European Journal, 2017, vol. 23, # 50, p. 12190 - 12197
[2] Synthesis (Germany), 2014, vol. 46, # 3, p. 348 - 356
[3] Angewandte Chemie - International Edition, 2004, vol. 43, # 29, p. 3814 - 3818
[4] Patent: WO2018/14802, 2018, A1, . Location in patent: Paragraph 0364
[5] Chemistry - A European Journal, 2013, vol. 19, # 29, p. 9452 - 9456
[6] Chemistry - An Asian Journal, 2011, vol. 6, # 10, p. 2816 - 2824
[7] Patent: CN105622638, 2016, A, . Location in patent: Paragraph 0328
[8] Patent: US9758545, 2017, B2, . Location in patent: Page/Page column 19; 20; 26
6
[ 75867-41-3 ]
[ 275386-60-2 ]
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).
Reference：
[1] Patent: EP2610243, 2013, A2, . Location in patent: Paragraph 0077; 0078; 0122; 0123
[2] Journal of the American Chemical Society, 2005, vol. 127, # 43, p. 15257 - 15264
7
[ 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 bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In tetrahydrofuran at 20℃;
A suspension of (4-iodophenyl)methanol (3.00 g, 13.64 mmol), ethynyltrimethylsilane (2.13 mL, 15.38 mmol), copper (_) iodide (122 mg, 0.64 mmol), bis(triphenylphosphine)palladium(II) dichloride (450 mg, 0.64 mmol), TEA (5.36 ml, 38.46 mmol) were stirred in THF (22 mL) at ambient temperature for overnight. The reaction solvent was evaporated under reduced pressure, and the residue was purified by column chromatography with hexane/ethyl acetate (20/1, v/v) to obtain the compound 53 (2.66 g, quant. yield): 1H NMR (400 MHz, CDCl3) _ 7.44 (d, J = 8.4 Hz, 2H), 7.26 (d, J = 8.5 Hz, 2H), 4.63 (s, 2H), 2.17 (bs, 1H), 0.25 (s, 9H); 13C NMR (100 MHz, CDCl3) _ 141.3, 132.2, 126.7, 122.4, 105.0, 94.3, 64.9, 0.1.
Reference：
[1] Patent: WO2018/160967, 2018, A1, . Location in patent: Page/Page column 86
[2] Journal of the American Chemical Society, 2015, vol. 137, # 45, p. 14319 - 14328
9
[ 77123-58-1 ]
[ 77123-57-0 ]
[ 229027-92-3 ]
[ 275386-60-2 ]
Reference：
[1] Journal of the American Chemical Society, 2000, vol. 122, # 19, p. 4817 - 4818
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).
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; tri-tert-butyl phosphine; In triethylamine; at 130℃; for 4h;Inert atmosphere; Microwave irradiation;
To a solution of (4-bromophenyl) methanol (935mg, 5mmol) in dry TEA was added Pd (PPh3) 2Cl2 (175mg, 0.25mmol) , CuI (48mg, 0.25mmol) and P (t-Bu) 3 (51mg, 0.25mmol) under N2 atmosphere. The reaction mixture was stirred for 5mins, followed by addition of ethynyltrimethylsilane (980mg, 10mmol) dropwise. The reaction mixture was then microwaved at 130 for 4hrs. The reaction mixture was cooled to room temperature, filtered over celite. Solvents were removed from the filtrate in vacuo, then the residue was extracted by EtOAc/H2O 3 times. The organic layer was combined, washed with brine, dried over Na2SO4 and further pufrified by silica gel column chromatography (PE/EA4/1) to give 670mg of (4- ( (trimethylsilyl) ethynyl) phenyl) methanol as a brown oil (66) .[0633]To a solution of (4- ( (trimethylsilyl) ethynyl) phenyl) methanol (250mg, 1.23mmol) in THF was added TBAF (500mg, 2.45mmol) in portions at 0. The reaction mixture was stirred at 0 to room temperature for 3hrs. Solvents were removed from the mixture in vacuo, and the residue was extracted by EtOAc/H2O 3 times. The organic layer was combined, washed with brine, dried over Na2SO4 and further pufrified by silica gel column chromatography (PE/EA4/1) to give 170mg of (4-ethynylphenyl) methanol as a brown oil (100) . 1H NMR (400Hz, CDCl3) delta7.45-7.49 (m, 2H) , 7.21-7.26 (m, 2H) , 4.69 (s, 1H) , 4.65 (s, 2H) .
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; In tetrahydrofuran; at 50℃; for 16h;Inert atmosphere;
4-bromobenzyl alcohol (3 g, 16 mmol, 1 eq.), cuprous iodide (0.3 g, 1.6 mmol, 0.1 eq) and bis(triphenylphosphine) palladium dichloride (0.57 g, 0.8 mmol, 0.05 eq.) was dissolved in tetrahydrofuran (50 ml) solution under nitrogen atmosphere. Added trimethylsilylacetylene (7.8 g, 80 mmol, 5 eq). Mixed system after the reaction at 50 C for 16 hours, and spin dry solvent under reduced pressure, the residue was purified by chromatography on silica gel column to give brown solid 4-trimethylsilylethynylbenzyl alcohol (1.5 g, crude).
1.274 g
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; diethylamine; triphenylphosphine; In N,N-dimethyl-formamide;Microwave irradiation; Heating; Inert atmosphere;
A solution of 4-Bromobenzyl alcohol (1.276 g, 6.82 mmol), Ethynyltrimethylsilane (1.061 ml, 7.51 mmol), PdCl2(PPh3)2 (24 mg, 0.034 mmol), Copper iodide (52 mg, 0.273 mmol), Triphenylphosphine (358 mg, 1.365 mmol), Diethylamine (10.70 ml, 102 mmol) in 2 ml of dry DMF (dimethylformamide) was heated under argon in a microwave oven at 150 C. for 30 min. The mixture was filtered. The filtrate was acidified with 1 M HCl and extracted 3 times with ether. The combined organic layers were washed with bicarbonate and water, dried over MgSO4 and concentrated to afford 3 (1.274 g, 6.23 mmol, 91% yield) as a brown solid.
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)
(1R,2S)-2-({4-[3,5-Bis-(4-[((1S,2R)-2-hydroxy-1-methyl-2-phenyl-ethyl)-methyl-amino]-methyl}-phenylethynyl)-phenylethynyl]-benzyl}-methyl-amino)-1-phenyl-propan-1-ol[ No CAS ]
Synthesis of Cvclopropyl-(4-trimethylsilanylethvnyl-benzyl)-amine (2). To a solution of compound 1 (1O g, 48.9 mmol) and DIEA (16 mL, 96.5 mmol) in CH2Cl2 (25 mL) at OC, was added methanesulfonyl chloride (4.56 mL, 58.7 mmol) dropwise. The solution was allowed to warm to ambient temperature and stirred for Ih. Cyclopropyl amine (25.69 g, 450 mmol) was added dropwise and resulting solution was stirred overnight at ambient temperature. The solution was concentrated in vacuo and the crude material was diluted with EtOAc (200 mL), washed with water (2 x 70 mL), brine (1 x 100 mL) and dried (Na2SO4), filtered and concentrated in vacuo. The crude material was purified by normal phase chromatography (120 g SiO2, CHCl3MeOH) to provide the desired compound 2 (3.6 g, 30 %) as brown liquid. LC-MS: [M+H]+=244.2; Ret. Time (Method A) 4.86 min.
With 1H-imidazole; In tetrahydrofuran; at 0 - 20℃; for 15h;Inert atmosphere;
[0079] Under argon condition, (4-((trimethylsilyl)ethynyl)phenyl) methanol (258 mg, 1.26 mmol) was dissolved in 5 mLof dry THF and then cooled to 0 C, and imidazole (103 mg, 1.52 mmol) and TBSCl (228 mg, 1.52 mmol) dissolved in3 mL of dry THF were added thereto. Thereafter, the temperature was raised to room temperature, and the reactionmixture was stirred for 15 hours at room temperature. Upon completion of the reaction, the reaction was terminated byadding 10 mL of aqueous saturated ammonium chloride solution. The reaction mixture was extracted with ethyl acetate(10 mL34), and the organic layer thus obtained was treated with anhydrous magnesium sulfate to remove water. Theprecipitate was filtered out and the resulting solution was concentrated by distillation under reduced pressure, and purifiedby column chromatography to obtain 383 mg (1.20 mmol, 95%) of the desired compound.[0080] 1H NMR (300 MHz, CDCl3): d 7.41 (d, 2H, J = 8.2 Hz), 7.23 (d, 2H, J = 8.1 Hz), 4.70 (s, 2H), 0.90 (s, 9H), 0.22(s, 9H), 0.00 (s, 6H).
Example 3 Synthesis of (4-((Trimethylsilyl)ethynyl)phenyl)methanol (3) A solution of 4-Bromobenzyl alcohol (1.276 g, 6.82 mmol), Ethynyltrimethylsilane (1.061 ml, 7.51 mmol), PdCl2(PPh3)2 (24 mg, 0.034 mmol), Copper iodide (52 mg, 0.273 mmol), Triphenylphosphine (358 mg, 1.365 mmol), Diethylamine (10.70 ml, 102 mmol) in 2 ml of dry DMF (dimethylformamide) was heated under argon in a microwave oven at 150 C. for 30 min. The mixture was filtered. The filtrate was acidified with 1M HCl and extracted 3 times with ether. The combined organic layers were washed with bicarbonate and water, dried over MgSO4 and concentrated to afford 3 (1.274 g, 6.23 mmol, 91% yield) as a brown solid.
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; In tetrahydrofuran; at 20℃;
A suspension of (4-iodophenyl)methanol (3.00 g, 13.64 mmol), ethynyltrimethylsilane (2.13 mL, 15.38 mmol), copper (_) iodide (122 mg, 0.64 mmol), bis(triphenylphosphine)palladium(II) dichloride (450 mg, 0.64 mmol), TEA (5.36 ml, 38.46 mmol) were stirred in THF (22 mL) at ambient temperature for overnight. The reaction solvent was evaporated under reduced pressure, and the residue was purified by column chromatography with hexane/ethyl acetate (20/1, v/v) to obtain the compound 53 (2.66 g, quant. yield): 1H NMR (400 MHz, CDCl3) _ 7.44 (d, J = 8.4 Hz, 2H), 7.26 (d, J = 8.5 Hz, 2H), 4.63 (s, 2H), 2.17 (bs, 1H), 0.25 (s, 9H); 13C NMR (100 MHz, CDCl3) _ 141.3, 132.2, 126.7, 122.4, 105.0, 94.3, 64.9, 0.1.
78%
With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); triethylamine; at 20℃; for 12h;
To a solution of 4-iodobenzyl alcohol (400 mg, 1.7 mmol), Pd(PPh3)4 (98 mg, 0.08 mmol), and CuI (14 mg, 0.008 mmol) in triethylamine(15 mL) was added ethynyltrimethylsilane (500 mg, 0.005 mol) at rt. After the reaction mixture was stirred at rt for 12 h, saturatedaq. NH4Cl was added, and the mixture was extracted with EtOAc. The combined organic phases were washed with brine, dried andconcentrated. Flash column chromatography with hexanes/EtOAc (5/1) as the eluent gave 4 (270 mg, 78%).
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