* 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 bromine; triphenylphosphine In dichloromethane at 0℃; for 1 h; Inert atmosphere
To a solution of triphenylphosphine (9.735 g, 37.11 mmol) in dry dichloromethane (46.0 mL) under N2, bromine (5.438 g, 34.03 mmol) was added at 0 °C. After 30 min, when the solution color changed from orange to white, compound 6 (3.960 g, 30.93 mmol) was slowly added. The mixture was stirred for 1 h, and then it was washed with water (3 × 30 mL) and a 10 percent aqueous solution of HCl (2 × 20 mL). The aqueous layer was extracted with ethyl acetate (3 × 20 mL), and then the combined organic layers was dried over Na2SO4 and concentrated in vacuum. The residue was purified by column chromatography, using hexane as eluent, to afford compound 7 in 70 percent yield (4.125 g, 21.6 mmol).
Reference:
[1] Angewandte Chemie - International Edition, 2014, vol. 53, # 31, p. 8122 - 8126
[2] Chemistry - A European Journal, 2011, vol. 17, # 49, p. 13692 - 13696
[3] Tetrahedron, 1996, vol. 52, # 35, p. 11601 - 11624
[4] Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 21, p. 6127 - 6130
[5] Bulletin de la Societe Chimique de France, 1993, vol. 130, # 2, p. 154 - 159
[6] Journal of the American Chemical Society, 1981, vol. 103, # 7, p. 1831 - 1835
[7] Journal of the Brazilian Chemical Society, 2013, vol. 24, # 12, p. 1933 - 1941
[8] Organic Letters, 2002, vol. 4, # 4, p. 485 - 488
[9] Journal of Medicinal Chemistry, 1984, vol. 27, # 10, p. 1351 - 1354
[10] Tetrahedron, 1994, vol. 50, # 31, p. 9425 - 9438
[11] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1982, p. 307 - 314
[12] Tetrahedron Letters, 1973, p. 3964 - 3966
[13] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1974, p. 1981 - 1987
[14] Synthetic Communications, 1972, vol. 2, p. 267 - 272
[15] J. Gen. Chem. USSR (Engl. Transl.), 1972, vol. 42, p. 710 - 711[16] Zhurnal Obshchei Khimii, 1972, vol. 42, p. 715
[17] Journal of Organometallic Chemistry, 1998, vol. 564, # 1-2, p. 61 - 70
[18] Tetrahedron Letters, 1999, vol. 40, # 43, p. 7605 - 7609
[19] Organic Letters, 2004, vol. 6, # 13, p. 2137 - 2140
[20] Journal of Organic Chemistry, 2000, vol. 65, # 26, p. 9152 - 9156
[21] Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999), 1987, p. 1077 - 1082
[22] European Journal of Organic Chemistry, 2009, # 21, p. 3605 - 3612
[23] ChemCatChem, 2013, vol. 5, # 10, p. 2939 - 2945
2
[ 75-77-4 ]
[ 106-96-7 ]
[ 38002-45-8 ]
Yield
Reaction Conditions
Operation in experiment
70%
Stage #1: With lithium hexamethyldisilazane In tetrahydrofuran; toluene at -78℃; for 0.5 h; Inert atmosphere Stage #2: for 0.5 h; Inert atmosphere
A solution of propargyl bromide (80percent in toluene, 6.69 mL, 60.0 mmol) in THF (75mL) was cooled to -78 °C under Ar. Lithium bis(trimethylsilyl)amide (10.37 g, 62.0mmol) was added under Ar, and the solution then stirred for 0.5 h. Chlorotrimethylsilane (10.15 mL, 80.0 mmol) was then added dropwise, and the solution stirred for 0.5 h, whereupon sat. NH4C1 (30 mL) was added, and the solution then warmed to RT. The solution was diluted with EtOAc, washed with brine, dried (MgSO4) and evaporated to give a crude oil. This was purified by Si02 chromatography (hexane as eluent), and then further purified by Kugelrohr distillation(70-90 °C, ambient pressure) to give compound 10 as a clear oil (8.09 g, 70percent): ‘H NIVIR (400 IVIHz; CDC13) 0.18 (s, 9H), 3.91 (s, 2H); ‘3C NIVIR (101 IVIHz; CDC13)-0.1, 14.9, 92.5, 100.2; JR (neat) v/cm’ 2960w, 2906w, 2180w, 1251m, 1204m, 1038m, 837s; MS(EJ): mlz = 174.9 [M-CH3].
Reference:
[1] Synthetic Communications, 1984, vol. 14, # 9, p. 805 - 816
[2] Patent: WO2018/29473, 2018, A1, . Location in patent: Page/Page column 51; 52
[3] Macromolecules, 2012, vol. 45, # 17, p. 6807 - 6818
[4] Journal of the American Chemical Society, 2012, vol. 134, # 30, p. 12751 - 12757
[5] Synthesis, 1985, # 5, p. 500 - 503
[6] Synthetic Communications, 1990, vol. 20, # 21, p. 3375 - 3378
[7] Tetrahedron, 1992, vol. 48, # 21, p. 4369 - 4378
[8] Journal of Organic Chemistry, 1996, vol. 61, # 20, p. 6906 - 6921
[9] Tetrahedron Letters, 2009, vol. 50, # 50, p. 6944 - 6946
[10] Patent: US5059695, 1991, A,
3
[ 36551-06-1 ]
[ 38002-45-8 ]
Reference:
[1] European Journal of Organic Chemistry, 2005, # 3, p. 582 - 592
[2] Journal of the Chemical Society - Perkin Transactions 1, 1998, # 11, p. 1839 - 1858
[3] Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999), 1987, p. 1077 - 1082
[4] Journal of the Brazilian Chemical Society, 2013, vol. 24, # 12, p. 1933 - 1941
With phosphorus tribromide In diethyl ether at 25℃; for 18.5h;
80%
With phosphorus tribromide at -5 - 20℃; Inert atmosphere;
79%
With pyridine; phosphorus tribromide In diethyl ether for 3h; Heating;
78%
With phosphorus tribromide In diethyl ether at 20℃; for 18.25h;
77%
With pyridine; phosphorus tribromide In diethyl ether a) -30 deg C, 2 h, b) 40 deg C, 30 min.;
75.2%
With bromine; triphenylphosphine In dichloromethane for 48h; Ambient temperature;
70%
With bromine; triphenylphosphine In dichloromethane at 0℃; for 1h; Inert atmosphere;
3-Bromo-1-trimethylsilylprop-1-yne (7)30
To a solution of triphenylphosphine (9.735 g, 37.11 mmol) in dry dichloromethane (46.0 mL) under N2, bromine (5.438 g, 34.03 mmol) was added at 0 °C. After 30 min, when the solution color changed from orange to white, compound 6 (3.960 g, 30.93 mmol) was slowly added. The mixture was stirred for 1 h, and then it was washed with water (3 × 30 mL) and a 10 % aqueous solution of HCl (2 × 20 mL). The aqueous layer was extracted with ethyl acetate (3 × 20 mL), and then the combined organic layers was dried over Na2SO4 and concentrated in vacuum. The residue was purified by column chromatography, using hexane as eluent, to afford compound 7 in 70 % yield (4.125 g, 21.6 mmol).
68%
With phosphorus tribromide In diethyl ether at 25℃; for 18h; Inert atmosphere;
66%
With N-Bromosuccinimide; triphenylphosphine In dichloromethane at -30℃; for 2h;
65%
With carbon tetrabromide; triphenylphosphine In diethyl ether for 1.5h;
43%
With bromine; triphenylphosphine In N,N-dimethyl-formamide for 18h; Ambient temperature;
30%
With bromine; triphenylphosphine In N,N-dimethyl-formamide for 18h; Ambient temperature;
With pyridine; dibromotriphenoxyphosphorane
With triphenylphosphine dibromide 1:1 addition complex In N,N-dimethyl-formamide
With pyridine; phosphorus tribromide
With phosphorus tribromide
With pyridine; phosphorus tribromide
With bromine; triphenylphosphine
With pyridine; phosphorus tribromide In diethyl ether
With bromine; triphenylphosphine In N,N-dimethyl-formamide at 20℃; for 2h;
Multi-step reaction with 2 steps
1: Et3N / CH2Cl2 / 0.25 h
2: LiBr / acetone / 1 h / Heating
With pyridine; phosphorus tribromide In diethyl ether at -70℃; Inert atmosphere;
With pyridine; bromine; triphenylphosphine In dichloromethane at 0 - 20℃;
With carbon tetrabromide; triphenylphosphine In dichloromethane for 2h;
With pyridine; phosphorus tribromide In diethyl ether at -40 - 20℃; for 25h;
With phosphorus tribromide In diethyl ether; dichloromethane at 20℃; Inert atmosphere;
With pyridine; phosphorus tribromide In diethyl ether at 20℃;
With copper(l) iodide; tetrabutylammomium bromide; sodium carbonate In N,N-dimethyl-formamide at 20℃;
Methyl 9-(trimethylsilyl)nona-5,8-diynoate (11)
The title compound was according to a literature procedure.1 To a mixture of Na2CO3 (1.66 g, 15.7 mmol,1.5 eq), CuI (1.98 g, 10.5 mmol, 1eq), n-Bu4NBr (1.01 g, 3.1 mmol, 0.3 eq) in DMF (12 ml) at -20 °C, 5-methyl hexynoate (9, 1.32 g, 10.5 mmol, 1eq) was added, followed by addition of 3-trimethylsilyl propagyl bromide (2.38 g, 12.5mmol, 1.2 eq). The reaction was allowed to stir at room temperature overnight. Et2O (5 ml) was added, and filtered through a short pad of silica gel. Water (10 ml) was added and the mixture was extracted with Et2O (3 x 20 ml). The organic layer was washed with saturated NH4Cl and dried (MgSO4). The solvent was evaporated and the residue was purified by flash chromatography (silica gel, hexane/EtOAc, 95:5) to afford the title compound (1.97 g, 80%) asa colorless oil which soon turned to yellow.
76%
With copper(l) iodide; tetrabutyl-ammonium chloride; sodium carbonate In N,N-dimethyl-formamide Ambient temperature;
75%
With copper(l) iodide; tetrabutyl-ammonium chloride; sodium carbonate In N,N-dimethyl-formamide at 20℃; for 16h;
With copper(l) iodide; caesium carbonate; sodium iodide In N,N-dimethyl-formamide at 20℃; for 16h;
Stage #1: 3-bromo-1-(trimethylsilyl)-1-propyne With magnesium In diethyl ether at 20℃; for 4h;
Stage #2: diphenylsilyl dichloride In diethyl ether at 0 - 20℃; for 12h;
Stage #3: allylmagnesium bromide In diethyl ether for 12h; Heating;
Stage #1: 4,5-diiodo-N,N-dimethyl-1H-imidazole-1-sulfonamide With ethylmagnesium bromide In diethyl ether; dichloromethane at 20℃; for 0.5h;
Stage #2: In tetrahydrofuran; diethyl ether; dichloromethane at 20℃;
Stage #3: 3-bromo-1-(trimethylsilyl)-1-propyne In tetrahydrofuran; diethyl ether; dichloromethane at -30 - 0℃; Further stages.;
D] 1-(3-Trimethylsilanyl-prop-2-ynyl)-cyclopropanecarboxylic acid tert-butyl ester A solution of 14.0 ml (2.0 M in THF/n-heptane/ethylbenzene, 28 mmol) LDA in 100 ml THF was treated during 15 min at -78 C. with 2.84 g (20 mmol) cyclopropanecarboxylic acid tert-butyl ester in 20 ml THF. After 6 h at -78 C., a solution of 3-(trimethylsilyl) propargyl bromide and 29 ml DMPU in 40 ml THF was added during 20 min. Over night, the solution was naturally warmed to room temperature, poured on ice/aqueous saturated NH4Cl solution and extracted with ether (three times). The organic phases were washed with aqueous 10% KHSO4, water (5*), aqueous 10% NaCl and dried (Na2SO4) to give 5.59 g of the title compound as volatile dark brown liquid. MS: 253.4(M+H)+.
methyl 1-(3-trimethylsilylprop-2-ynyl)triazole-4-carboxylate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
33%
Preparation 11Synthesis of methyl l-(3-trimethylsilyl rop-2-ynyl)triazole-4-carboxylate.Place methyl lH-triazole-5-carboxylate (400.00 mg, 3.15 mmoles) and dimethylformamide (6.84 mL) in a round bottom flask. Cool the mixture to 0 °C. Add sodium hydride (120.00 mg, 3.0 mmoles) portionwise over 20 minutes and then stir for 20 minutes. Add 3-bromoprop-l-ynyl(trimethyl)silane (578.83 mu, 4.09 mmoles). Quench the reaction with water and extract three times with ethyl acetate. Wash one time with brine and dry over sodium sulfate, filter and concentrate under reduced pressure. The residue is purified by normal phase chromatography using ethyl acetate/hexane to give the title compound (0.25 g, 33percent). LCMS (m/z): 238.0 (M+l).
(4,4-bis(phenylsulfonyl)but-1-yn-1-yl)trimethylsilane[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
52%
Stage #1: bis(phenylsulfonyl)methane With tetra-(n-butyl)ammonium iodide; sodium hydride In N,N-dimethyl-formamide at 0℃; for 0.5h; Inert atmosphere;
Stage #2: 3-bromo-1-(trimethylsilyl)-1-propyne In N,N-dimethyl-formamide at 20℃; for 2h; Inert atmosphere;
(4,4-bis(phenylsulfonyl)but-1-yn-1-yl)trimethylsilane (3a’)
To a stirred suspension of sodium hydride (618 mg, 15.5 mmol, 1.0 equiv) and tetrabutylammonium iodide (0.5708 g, 1.55 mmol, 0.1 equiv) in DMF was added bis(phenylsulfonyl)methane (9) (4.58 g, 15.5 mmol, 1.0 equiv) in DMF (15 mL) at 0 °C, and the reaction mixture was stirred for 30 min at 0 °C. Then, to a stirred solution, 3-bromo-1-trimethylsilylprop-1-yne (3.2495 g, 17.0 mmol, 1.1 equiv) in DMF was added and the resultant mixture was stirred at room temperature for 2 h. To the reaction mixture was added saturated aqueous NH4Cl solution (30 mL). The aqueous layer was extracted with Et2O (20 mL×3), and the combined organic layer was dried over Na2SO4, and evaporated. The residue was purified by silica gel flash column chromatography (hexane/ethyl S4 acetate = 10/1) to afford 3a’ (3.26 g, 52%) as a white powder: Rf = 0.25 (hexane/ethyl acetate = 4/1); 1H NMR (500 MHz, CDCl3) δ 8.00 (4H, d, J = 8.3 Hz), 7.72 (2H, dd, J = 8.3, 8.3 Hz), 7.59 (4H, dd, J = 8.3, 8.3 Hz), 4.59 (1H, t, J = 6 Hz), 3.17 (2H, d, J = 6.0 Hz), 0.06 (9H, s); 13C NMR (125 MHz, CDCl3) δ 137.8, 134.8, 129.8, 129.1, 98.5, 89.1, 82.3, 17.9, -0.3; IR (neat) νmax 3066, 2957, 2183, 1584, 1448, 1323, 1312, 1078, 998, 841, 756, 685, 573 cm-1; HRMS-ESI [M+Na]+ calculated for C19H22O4NaS2Si: 429.0621, found: 429.0620; mp 83.9 - 84.8 °C.
tert-butyl 3-cyano-3-[3-(trimethylsilyl)prop-2-yn-1-yl]azetidine-1-carboxylate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
84%
To a solution of tert-butyl3-cyanoazetidine-1-carboxylate (22) (100 mg, 0.549 mmol, 1 equiv.) in dry THF (2 mL) was added LiHMDS (1Min THF, 0.549 mL, 0.549 mmol, 1 equiv.) at -78 oC and stirred for 30 min. at the same temperature. 3-Bromo-1-(trimethylsilyl)propyne (0.107 mL, 0.659 mmol, 1.2 equiv.) was added via syringe and stirred at -78 oC for 30min. followed by stirring at rt overnight. The resulting mixture was quenched with NH4Cl (2 mL) and extractedwith ethyl acetate (3 x 5 mL). The combined organic extracts were washed with brine (3 mL), dried overNa2SO4, and concentrated. The crude material was purified by flash chromatography (silica gel, 5-40% EtOAc inhexanes) to give the desired product 30 (126.4 mg, 84%). Physical State: white solid (mp 83-84 oC); Rf = 0.7(3:7 EtOAc/hexanes, vis. KMnO4); 1H NMR (500 MHz, CDCl3): delta 4.24 (d, J 8.8 Hz, 2H), 4.00 (d, J 8.8 Hz, 2H), 2.79(s, 2H), 1.45 (s, 9H), 0.17 (s, 9H); 13C NMR (126 MHz, CDCl3): delta 155.5, 120.7, 98.3, 90.2, 80.9, 56.9 (br, 2C), 29.8,28.4 (3C), 27.8, -0.1 (9C).
With magnesium; In tetrahydrofuran; at 20℃; for 0.333333h;Inert atmosphere;
General procedure: In a 200 mL three necked flask equipped with a dropping funnel, a THF solution of S2 (1.0 equiv.)was slowly added to a mixture of Mg (1.1 equiv., pre-activated by stirring for several hours in vacuo)and THF. A THF solution of alkyne (1.1 equiv.) was subsequently added, and the reaction mixturewas stirred at room temperature. Then, HCl aq. (1M) was added, and the resultant solution wasextracted with Et2O. The organic layer was washed with Brine, dried over anhydrous Na2SO4,filtered, and concentrated in vacuo to yield a crude product including S3. If needed, the purificationwas performed by a column chromatography on a silica gel (eluted with 510% EtOAc/hexane).
Stage #1: ethyl 4-nitrobutanoate With N,N-diisopropyl-1,2-ethanediamine; potassium <i>tert</i>-butylate; copper(I) bromide In 1,4-dioxane at 20℃; for 0.5h; Schlenk technique; Inert atmosphere;
Stage #2: 3-bromo-1-(trimethylsilyl)-1-propyne In 1,4-dioxane at 20℃; for 4h; Schlenk technique; Inert atmosphere;