* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Reference：
[1] Tetrahedron, 2007, vol. 63, # 40, p. 9979 - 9990
[2] Organic Letters, 2012, vol. 14, # 19, p. 5062 - 5065,4
[3] Journal of Organic Chemistry, 2003, vol. 68, # 5, p. 1843 - 1851
[4] Journal of Organic Chemistry, 2018, vol. 83, # 12, p. 6673 - 6680
5
[ 107793-07-7 ]
[ 33577-99-0 ]
Yield
Reaction Conditions
Operation in experiment
96%
With cesium fluoride In water; acetonitrile at 20℃; for 4 h;
Preparation 28; 2-Ethynyl-benzoic acid methyl ester; To a solution of 2-trimethylsilanylethynyl-benzoic acid methyl ester (540 mg, 2.32 mmol) in acetonitrile/water (20 mL/5 mL) is added cesium fluoride (1.41 g, 9.30 mmol). The reaction is stirred at room temperature. After 4 h, the reaction is concentrated and the residue is partitioned between EtOAc (100 mL) and 0.2N HCl (30 mL). The aqueous layer is extracted with EtOAc (100 mL) and the combined organic layers are washed with brine, dried (MgSO4), filtered, and concentrated. The residue is chromatographed eluting with 0 to 5 percent EtOAc/Hexanes to yield the title compound (358 mg, 96 percent). GC/MS: 160.
74%
With potassium trimethylsilonate In dimethyl sulfoxide at 60℃; for 12 h; Sealed tube
Methyl 2-[(trimethylsilyl)ethynyl]benzoate (1 mmol), inorganic base potassium tert-butoxide (sodium) or potassium hydroxide (sodium) or potassium trimethylsilylate (sodium) (0.05 (2 mmol), 2 mL of DMA or DMSO solvent was added in turn to a 10 mL sealed tube, and the mixture was heated and stirred in a 60°C oil bath for 12 hours. The progress of the reaction was followed by TLC. The reaction was completed and an equivalent of mesitylene or tetradecane was added to the crude product. Alkane was used as an internal standard to determine the exact yield of the product by GC and GC-MS. According to GC and GC-MS, when DMSO is used as a reaction solvent, inorganic base potassium tert-butoxide (sodium) or potassium hydroxide (sodium) or potassium trimethylsilylate (sodium) is used as a catalyst, and the yields of the products are as follows: 48percent, 56percent, 50percent, 49percent, 74percent, 71percent. When DMA was used as the reaction solvent, the inorganic potassium tert-butoxide (sodium) or potassium hydroxide (sodium) or potassium trimethylsilylate (sodium) was used as a catalyst. The yields of the products were: 39percent, 42percent, respectively. 40percent, 41percent, 62percent, 59percent.
33%
With potassium carbonate In methanol for 4 h; Inert atmosphere
[00093] To a stirred solution of compound 43 (45 g, 193.96 mmol) in MeOH (500 mL) under inert atmosphere was added potassium carbonate (40 g, 290.94 mmol) at RT and stirred for 4 h. The reaction was monitored by TLC; after completion of the reaction, the reaction mixture was filtered through celite washed with CH2CI2 (2 x 500 mL). The filtrate was removed in vacuo to obtain the crude. The crude was as purified through silica gel column chromatography using 2percent EtOAc/ hexanes to afford compound 44 (31 g, 33percent) as colorless syrup. TLC: 5percent EtOAc/ hexanes (R/. 0.5); 1H NMR (CDC13, 400 MHz): δ 7.97-7.91 (m, 1H), 7.62 (dd, J= 7.7, 1.1 Hz, 1H), 7.47 (td, J = 7.6, 1.5 Hz, 1H), 7.40 (td, J= 7.7, 1.4 Hz, 1H), 3.38 (s, 1H), 3.91 (s, 3H).
Reference：
[1] Tetrahedron Letters, 2003, vol. 44, # 46, p. 8525 - 8527
[2] Tetrahedron, 2007, vol. 63, # 40, p. 9979 - 9990
[3] Patent: WO2007/140174, 2007, A2, . Location in patent: Page/Page column 32
[4] Organic Letters, 2010, vol. 12, # 16, p. 3651 - 3653
[5] Tetrahedron Letters, 2010, vol. 51, # 15, p. 2007 - 2009
[6] Organic and Biomolecular Chemistry, 2014, vol. 12, # 40, p. 7937 - 7941
[7] Journal of the American Chemical Society, 2016, vol. 138, # 7, p. 2126 - 2129
[8] Angewandte Chemie - International Edition, 2016, vol. 55, # 46, p. 14286 - 14290[9] Angew. Chem., 2016, vol. 128, # 46, p. 14498 - 14502,5
[10] Journal of Organic Chemistry, 2003, vol. 68, # 5, p. 1843 - 1851
[11] Journal of Organic Chemistry, 2009, vol. 74, # 3, p. 1141 - 1147
[12] Angewandte Chemie - International Edition, 2016, vol. 55, # 37, p. 11292 - 11295[13] Angew. Chem., 2016, vol. 128, # 37, p. 11462 - 11465,4
[14] Organic Letters, 2012, vol. 14, # 19, p. 5062 - 5065,4
[15] Patent: CN107459438, 2017, A, . Location in patent: Paragraph 0078; 0079
[16] Journal of the Chinese Chemical Society, 2008, vol. 55, # 3, p. 643 - 648
[17] Tetrahedron, 1998, vol. 54, # 37, p. 11209 - 11234
[18] Patent: WO2017/48954, 2017, A1, . Location in patent: Paragraph 00093
[19] Journal of Chemical Research, Miniprint, 1986, # 10, p. 3020 - 3036
[20] Synlett, 2003, # 11, p. 1603 - 1606
[21] Organic Letters, 2002, vol. 4, # 26, p. 4663 - 4666
[22] Advanced Synthesis and Catalysis, 2008, vol. 350, # 9, p. 1248 - 1252
[23] Organic Letters, 2015, vol. 17, # 10, p. 2522 - 2525
[24] Journal of the American Chemical Society, 2017, vol. 139, # 21, p. 7184 - 7187
[25] European Journal of Organic Chemistry, 2017, vol. 2017, # 36, p. 5343 - 5346
6
[ 33577-96-7 ]
[ 33577-99-0 ]
Reference：
[1] Synthetic Communications, 2013, vol. 43, # 20, p. 2809 - 2816
[2] Journal of Organic Chemistry, 1985, vol. 50, # 10, p. 1763 - 1765
[3] Journal of Organic Chemistry, 1992, vol. 57, # 18, p. 4940 - 4948
[4] Journal of Medicinal Chemistry, 2004, vol. 47, # 6, p. 1475 - 1486
[5] Journal of Molecular Structure, 2017, vol. 1138, p. 81 - 89
7
[ 229028-09-5 ]
[ 33577-99-0 ]
Reference：
[1] Organic Letters, 2016, vol. 18, # 4, p. 812 - 815
[2] Catalysis Science and Technology, 2016, vol. 6, # 6, p. 1946 - 1951
8
[ 610-97-9 ]
[ 74-86-2 ]
[ 33577-99-0 ]
Reference：
[1] Tetrahedron, 2004, vol. 60, # 31, p. 6685 - 6688
[2] Journal of Organic Chemistry, 2018, vol. 83, # 12, p. 6673 - 6680
9
[ 610-97-9 ]
[ 33577-99-0 ]
Reference：
[1] Tetrahedron, 2007, vol. 63, # 40, p. 9979 - 9990
[2] Journal of Medicinal Chemistry, 2004, vol. 47, # 6, p. 1475 - 1486
[3] Synlett, 2003, # 11, p. 1603 - 1606
[4] Journal of Organic Chemistry, 2003, vol. 68, # 5, p. 1843 - 1851
[5] Tetrahedron, 1998, vol. 54, # 37, p. 11209 - 11234
[6] Doklady Chemistry, 1985, vol. 283, p. 212 - 214[7] Dokl. Akad. Nauk SSSR Ser. Khim., 1985, vol. 283, # 3, p. 630 - 633
[8] Organic Letters, 2015, vol. 17, # 10, p. 2522 - 2525
[9] Journal of the American Chemical Society, 2016, vol. 138, # 7, p. 2126 - 2129
[10] Angewandte Chemie - International Edition, 2016, vol. 55, # 46, p. 14286 - 14290[11] Angew. Chem., 2016, vol. 128, # 46, p. 14498 - 14502,5
[12] Angewandte Chemie - International Edition, 2016, vol. 55, # 37, p. 11292 - 11295[13] Angew. Chem., 2016, vol. 128, # 37, p. 11462 - 11465,4
[14] Journal of Molecular Structure, 2017, vol. 1138, p. 81 - 89
[15] Patent: WO2007/140174, 2007, A2,
10
[ 610-94-6 ]
[ 33577-99-0 ]
Reference：
[1] Tetrahedron Letters, 2003, vol. 44, # 46, p. 8525 - 8527
[2] Organic Letters, 2002, vol. 4, # 26, p. 4663 - 4666
[3] Journal of Organic Chemistry, 1992, vol. 57, # 18, p. 4940 - 4948
[4] Journal of Organic Chemistry, 1985, vol. 50, # 10, p. 1763 - 1765
[5] Organic Letters, 2012, vol. 14, # 19, p. 5062 - 5065,4
[6] Synthetic Communications, 2013, vol. 43, # 20, p. 2809 - 2816
[7] Patent: WO2017/48954, 2017, A1,
[8] Journal of the American Chemical Society, 2017, vol. 139, # 21, p. 7184 - 7187
[9] European Journal of Organic Chemistry, 2017, vol. 2017, # 36, p. 5343 - 5346
11
[ 610-97-9 ]
[ 1066-54-2 ]
[ 33577-99-0 ]
Reference：
[1] Journal of the American Chemical Society, 2014, vol. 136, # 17, p. 6255 - 6258
With potassium hydroxide; In toluene; for 2h;Reflux; Inert atmosphere;
General procedure: A mixture of 1a or 2a or 5b (1 eq) and potassium hydroxide (1eq) in toluenewas heated under reflux for 2 h in argon atmosphere.The reaction mixture was cooled, filtered, extracted with ethyl acetateand washed with 0.1 M KHSO4 and water. Organic layer wasdried over anhydrous magnesium sulfate, filtered and the solventwas evaporated The pure products were isolated by multiplecrystallization from a mixture of petroleum ether and ethyl acetate(1b and 2b) or by column chromatography on silica gel (petroleumether/ethyl acetate 10:1 (v/v) (5c)).
With cesium fluoride; In water; acetonitrile; at 20℃; for 4h;
Preparation 28; 2-Ethynyl-benzoic acid methyl ester; To a solution of 2-trimethylsilanylethynyl-benzoic acid methyl ester (540 mg, 2.32 mmol) in acetonitrile/water (20 mL/5 mL) is added cesium fluoride (1.41 g, 9.30 mmol). The reaction is stirred at room temperature. After 4 h, the reaction is concentrated and the residue is partitioned between EtOAc (100 mL) and 0.2N HCl (30 mL). The aqueous layer is extracted with EtOAc (100 mL) and the combined organic layers are washed with brine, dried (MgSO4), filtered, and concentrated. The residue is chromatographed eluting with 0 to 5 % EtOAc/Hexanes to yield the title compound (358 mg, 96 %). GC/MS: 160.
95%
With methanol; potassium carbonate; at 20℃; for 3h;
To a solution of methyl 2-((trimethylsilyl) ethynyl) benzoate (33) (2.0 g, 8.6 mmol) in methanol (45 mL),Potassium carbonate (2.3 g, 17 mmol) was added andThe mixture was stirred at room temperature for 3 hours. Saturated aqueous ammonium chloride solution (30 mL) was added to the reaction solution,Extraction was performed using diethyl ether (30 mL × 3).The organic layer was dried over magnesium sulfate and concentrated under reduced pressure.The obtained residue isPurified by silica gel column chromatography (ethyl acetate: hexane = 1: 8),Methyl 2-ethynyl benzoate (30)(1.3 g, 8.2 mmol, 95%)Was obtained as a red oil.
82.6%
With cesium fluoride; In water; acetonitrile; at 20℃;
23 g (99 mmol) of [1919-d] in a 1 L round bottom flask,230 ml of acetonitrile,Add 50ml water and cesium fluoride 45.1g (297mmol)After the reaction was stirred at room temperature and the reaction was terminated by TLC,After the reaction was completed, the reaction solution was extracted with ethyl acetate and 0.2N hydrochloric acid.The organic layer was separated and purified by a column to obtain 18 g (yield: 82.6%) of the compound represented by [Formula 191-e].
74%
With potassium trimethylsilonate; In dimethyl sulfoxide; at 60℃; under 760.051 Torr; for 12h;Sealed tube;Catalytic behavior;
Methyl 2-[(trimethylsilyl)ethynyl]benzoate (1 mmol), inorganic base potassium tert-butoxide (sodium) or potassium hydroxide (sodium) or potassium trimethylsilylate (sodium) (0.05 (2 mmol), 2 mL of DMA or DMSO solvent was added in turn to a 10 mL sealed tube, and the mixture was heated and stirred in a 60C oil bath for 12 hours. The progress of the reaction was followed by TLC. The reaction was completed and an equivalent of mesitylene or tetradecane was added to the crude product. Alkane was used as an internal standard to determine the exact yield of the product by GC and GC-MS. According to GC and GC-MS, when DMSO is used as a reaction solvent, inorganic base potassium tert-butoxide (sodium) or potassium hydroxide (sodium) or potassium trimethylsilylate (sodium) is used as a catalyst, and the yields of the products are as follows: 48%, 56%, 50%, 49%, 74%, 71%. When DMA was used as the reaction solvent, the inorganic potassium tert-butoxide (sodium) or potassium hydroxide (sodium) or potassium trimethylsilylate (sodium) was used as a catalyst. The yields of the products were: 39%, 42%, respectively. 40%, 41%, 62%, 59%.
33%
With potassium carbonate; In methanol; for 4h;Inert atmosphere;
[00093] To a stirred solution of compound 43 (45 g, 193.96 mmol) in MeOH (500 mL) under inert atmosphere was added potassium carbonate (40 g, 290.94 mmol) at RT and stirred for 4 h. The reaction was monitored by TLC; after completion of the reaction, the reaction mixture was filtered through celite washed with CH2CI2 (2 x 500 mL). The filtrate was removed in vacuo to obtain the crude. The crude was as purified through silica gel column chromatography using 2% EtOAc/ hexanes to afford compound 44 (31 g, 33%) as colorless syrup. TLC: 5% EtOAc/ hexanes (R/. 0.5); 1H NMR (CDC13, 400 MHz): delta 7.97-7.91 (m, 1H), 7.62 (dd, J= 7.7, 1.1 Hz, 1H), 7.47 (td, J = 7.6, 1.5 Hz, 1H), 7.40 (td, J= 7.7, 1.4 Hz, 1H), 3.38 (s, 1H), 3.91 (s, 3H).
272 mg
With potassium carbonate; In methanol; at 23℃; for 2h;
Under argon, an oven-dried 25-mL flask was charged with methyl 2-bromobenzoate (0.43 g, 2.0 mmol, 1 .0 equiv) and Et3N/THF (2.0 mL, 10:1 (v/v), c = 1 .0 M), to which PdCI2(PPh3)2(70 mg, 0.10 mmol, 5.0 mol%) and Cul (19 mg, 0.10 mmol, 5.0 mol%) were added. The resulting yellow heterogeneous mixture was cooled to 0 C in an ice-water bath and stirred at 0 C for 30 min. Trimethylsilylacetylene (0.39 g, 0.56 mL, 4.0 mmol, 2.0 equiv) was then added within 1 min. Subsequently, the flask was moved from the ice- water bath and heated at 90 C for 12 h. After cooling to 23 C, the volatiles were evaporated under reduced pressure. The dark oil obtained was diluted with 2.0 mL water, and the mixture was extracted with hexane/Et20 10:1 (v/v). The organic phase was separated, dried by Na2S04and then concentrated under reduced pressure. MeOH (2.0 mL) and K2C03(0.28 g, 2.0 mmol, 1.0 equiv) were added to the residue, and the resulting mixture was stirred at 23 C for 2 h. The solvent was then evaporated, and the resulting residue was purified by flash column chromatography on silica gel, eluting with EtOAc/hexane 1 :10 (v/v) to afford 272 mg (55%) of the title compound as yellow oil.Rf = 0.30 (EtOAc/hexanes 1 :8 (v/v)).NMR Spectroscopy:1H NMR (500 MHz, CDCI3, 23 C, delta): 7.95 - 7.93 (m, 1 H), 7.63 - 7.61 (m, 1 H), 7.49 - 7.45 (m, 1 H), 7.42 - 7.38 (m, 1 H), 3.93 (s, 3H), 3.39 (s, 1 H).13C NMR (125 MHz, CDCI3, 23 C, delta): 166.6, 135.1 , 132.6, 131 .8, 130.4, 128.6, 122.8, 82.4, 82.1 , 52.3.H RMS-El (m/z) calc'd for Ci0H8O2[M]+, 160.0519, found: 160.0520.
With iron(III) chloride; In DCE; at 80℃;Inert atmosphere;
General procedure: A mixture of o-(1-alkynyl)benzoates 1 (0.2 mmol), disulfides 2 (0.2 mmol), FeCl3(0.2 mmol), and anhydrous DCE (2 mL) was stirred in a Schlenk tube at 80 C (oil bath temperature) under N2 atmosphere until complete consumption of starting material as monitored by TLC (usually 20-24 h), the mixture was diluted by dichloromethane (10 mL), washed with saturated brine (3×10 mL), and dried over Na2SO4, Evaporation of the solvent followed by purification on silica gel (eluting with PE/EA=100:1 to 30:1) provides the pure product 3.
methyl 2-((2-amino-4-benzamidophenyl)ethynyl)benzoate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
56%
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; In N,N-dimethyl-formamide; at 70℃; for 2h;Inert atmosphere;
A solution of 10 (0.031 g, 0.0917 mmol) and methyl 2-alkynylbenzoate 6 (0.0176 g, 0.110 mmol) in N,N-dimethylformamide (1.0 mL) and triethylamine (1.0 mL) was degassed by nitrogen stream for 10 min. Bis(triphenylphosphine)palladium(II) dichloride (0.0038 g, 0.0055 mmol) and copper(I) iodide (0.0017 g, 0.0092 mmol) were added and the mixture was heated to 70 C. The reaction was allowed to stir for 2 h then diluted with ethyl acetate and washed with water. The organic layer was dried and concentrated in vacuo. The product was purified by column chromatography on silica gel (2:1 hexanes/ethyl acetate) to give the title compound 11 (0.019 g, 56 %) as a yellow solid; 1H-NMR (500 MHz, CDCl3): deltaH 8.03 (d, J 7.9, 1H), 7.85 (d, J 7.1,2H), 7.65 (d, J 7.7, 1H), 7.55 (t, J 7.4, 1H), 7.52 (d, J 8.0, 1H), 7.48 (t, J 7.6, 2H), 7.42 (s, 1H), 7.34 (m, 2H), 6.74 (d, J 8.3, 2H), 5.17 (s, 2H), 3.94 (s, 3H); 13C-NMR (125 MHz, CDCl3): deltaC 166.4, 165.8, 150.9, 139.9, 135.1, 133.6, 132.8, 132.2, 132.0, 130.7, 128.9, 127.3, 127.1, 124.9, 108.8, 104.9, 103.4,93.7, 92.8, 52.4; HRMS: found 371.1262; C23H19N2O3+ [M+H]+ requires 371.1317.
With copper(II) sulfate; sodium L-ascorbate; In tetrahydrofuran; at 20℃;Inert atmosphere;
To a solution of compound 4 (79.7 mg, 0.1 mmol) and 2-carboxymethylphenylacetylene(24.0 mg, 0.15 mmol) under argon,Intetrahydrofuran (3 mL) was quickly added 0.38 mL of CuSO4 (1.0Maq) and 0.75 mLof sodium ascorbate (1.0 M aq), and the reaction was allowed to proceed at roomtemperature overnight. The organic phase was separated by filtration, and theorganic phase was separated. The organic phase was diluted with ethyl acetate(15 mL) and washed with 10 mL of saturated brine three times. The organic phasewas dried, filtered and subjected to column chromatography to give compound 5i(48.9 mg, yield 51 %).
methyl (Z)-2-(4-chlorobut-3-en-1-yn-1-yl)benzoate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
55%
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; N-butylamine; In diethyl ether; at 20℃; for 7h;Inert atmosphere;
The protocol was identical to that developed for (E)-4, but n-BuNH2 (200 muL mg, 2 mmol) replaced piperidine and (Z)-1,2-dichloroethylene (800 muL, 20 mmol) was used. The crude was purified by chromatography on SiO2 to give (Z)-4 (114 mg, 0.52 mmol, 55%) as a brown oil. IR (neat): 3087, 2951, 1729, 1711, 1582, 1565, 1484, 1447, 1432,1335, 1294, 1277, 1252, 1190, 1164, 1128, 1083, 1043, 962, 831, 801,756, 724, 697, 660, 634 cm-1 . 1H NMR (300 MHz, CDCl3): delta = 7.95 (d, J = 7.8 Hz, 1 H), 7.61 (d, J = 7.8Hz, 1 H), 7.47 (td, J = 7.6 Hz, J = 1.2 Hz, 1 H), 7.37 (td, J = 7.6 Hz, J = 1.2Hz, 1 H), 6.47 (d, J = 7.5 Hz, 1 H), 6.16 (d, J = 7.5 Hz, 1 H), 3.93 (s, 3 H). 13C NMR (75 MHz, CDCl3): delta = 166.6 (Cq), 134.4 (CH), 131.8 (Cq),131.7 (CH), 130.4 (CH), 128.8 (CH), 128.4 (CH), 123.1 (Cq), 112.3 (CH), 96.0 (Cq), 88.0 (Cq), 52.3 (CH3). HRMS: m/z [M + H]+ calcd for C12H10O2Cl: 221.0369; found: 221.0363.
With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); N-butylamine; In diethyl ether; at 20℃; for 6h;
General procedure: To a stirred solution of 1,2-diiodobenzene (4.95 g, 15 mmol) in Et2O (100 mL) containing Pd(PPh3)4 (0.75 g, 0.625 mmol) was added methyl 2-ethynylbenzoate (2) (2.0 g, 12.5 mmol), CuI (0.24 g, 1.0 mmol) and n-BuNH2 (1.83 g, 12.3 mmol). The resulting solution was stirred at room temperature for 6 h, quenched by saturated aqueous NH4Cl (100 mL), and extracted by EtOAc (100 mL 2). The combined organic layers were dried over MgSO4. After filtration and removal of EtOAc, the residue was purified by column chromatography on silica gel to give methyl 2-((2-iodophenyl)ethynyl)benzoate (3) (3.7 g. 82%).
General procedure: Appropriate halogenoarene (1 eq) was dissolved in triethylamine(TEA) and the solution was cooled to 0 C. Then a traceamount of copper iodide and bis(triphenylphosphine)palladium(II)dichloride, Pd[(C6H5)3P]2Cl2 as catalysts were added. After a fewminutes acetylene derivative (2 eq) was added. The reactionmixture was stirred for about 9 h and then was filtered, extracted with ethyl acetate andwashed withwater. Combined organic layerswas dried over anhydrous magnesium sulfate, filtered and thesolvent was evaporated. The pure products 1a-2a were isolated by:crystallization from a mixture of ethyl acetate and petroleum ether(1a) and ethyl acetate (2a) or by column chromatography on silicagel (petroleum ether/ethyl acetate 20:1 (v/v) (5b)).
General procedure: Appropriate halogenoarene (1 eq) was dissolved in triethylamine(TEA) and the solution was cooled to 0 C. Then a traceamount of copper iodide and bis(triphenylphosphine)palladium(II)dichloride, Pd[(C6H5)3P]2Cl2 as catalysts were added. After a fewminutes acetylene derivative (2 eq) was added. The reactionmixture was stirred for about 9 h and then was filtered, extracted with ethyl acetate andwashed withwater. Combined organic layerswas dried over anhydrous magnesium sulfate, filtered and thesolvent was evaporated. The pure products 1a-2a were isolated by:crystallization from a mixture of ethyl acetate and petroleum ether(1a) and ethyl acetate (2a) or by column chromatography on silicagel (petroleum ether/ethyl acetate 20:1 (v/v) (5b)).
methyl 2-[(1E)-2-cyanoeth-1-en-1-yl]benzoate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
78%
With 1,1'-bis-(diphenylphosphino)ferrocene; (hydridotris(1-pyrazolyl)borato)(1,5-cyclooctadiene)rhodium(I); In acetonitrile; at 110℃; for 12h;Inert atmosphere; Sealed tube; Glovebox;
In an anhydrous, argon-filled glovebox, a 4 ml. vial was charged with TpRh(COD) (6.3 mg, 15 muetaiotaomicronIota, 7.5 mol%), dppf (8.3 mg, 15 muetaiotaomicronIota, 7.5 mol%), and MeCN (1.0 ml_, c = 0.2 M). Methyl 2-ethynylbenzoate (32.0 mg, 0.200 mmol, 1 .00 equiv) and acetone cyanohydrin (17.0 mg, 19.5 muIota_, 0.200 mmol, 1.00 equiv) were then added to the reaction mixture. The vial was sealed with a Teflon cap and moved from the glovebox to a preheated metal heating block (1 10 C). The reaction mixture was then stirred at 1 10 C for 12 hours. After cooling to 23 C, the resulting mixture was filtered through a short plug of silica gel, eluting - - with EtOAc. The filtrate was collected and concentrated in vacuo. The resulting residue was purified by flash column chromatography on silica gel, eluting with EtOAc/hexane 1 :6 (v/v) to afford 29.1 mg (78%) of the title compound as yellow solid.Rf = 0.40 (EtOAc/hexanes 1 :6 (v/v)).NMR Spectroscopy:1H NMR (500 MHz, CDCI3, 23 C, delta): 8.31 (d, J = 16.5 Hz, 1 H), 8.01 (dd, J = 7.5, 1.5 Hz, 1 H), 7.57 - 7.49 (m, 3H), 5.77 (d, J = 16.5 Hz, 1 H), 3.94 (s, 3H).13C NMR (125 MHz, CDCI3, 23 C, delta): 166.8, 150.2, 135.5, 132.8, 131 .3, 130.4, 129.3, 127.4, 1 17.9, 99.2, 52.7.HRMS-FIA (m/z) calc'd for Cn H9N02[M]+, 187.0627; found: 187.0628.
methyl 2-((2-iodophenyl)ethynyl)benzoate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
82%
With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); N-butylamine; In diethyl ether; at 20℃; for 6h;
To a stirred solution of 1,2-diiodobenzene (4.95 g, 15 mmol) in Et2O (100 mL) containing Pd(PPh3)4 (0.75 g, 0.625 mmol) was added methyl 2-ethynylbenzoate (2) (2.0 g, 12.5 mmol), CuI (0.24 g, 1.0 mmol) and n-BuNH2 (1.83 g, 12.3 mmol). The resulting solution was stirred at room temperature for 6 h, quenched by saturated aqueous NH4Cl (100 mL), and extracted by EtOAc (100 mL 2). The combined organic layers were dried over MgSO4. After filtration and removal of EtOAc, the residue was purified by column chromatography on silica gel to give methyl 2-((2-iodophenyl)ethynyl)benzoate (3) (3.7 g. 82%).
methyl 2-((2-carbamoyl-4,5-dimethoxyphenyl)ethynyl)benzoate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
97%
With bis-triphenylphosphine-palladium(II) chloride; triethylamine; In acetonitrile; at 80℃;Inert atmosphere;
General procedure: To a solution of 2-halobenzamide (2.0 mmol, 1.0 equiv) in MeCN (13 mL) were added PdCl2(PPh3)2 (0.05 equiv), terminal alkyne (1.2 equiv.), and Et3N (3.0 equiv.). The resulting mixture was stirred at 80 C under argon. The progress of the reaction was monitored by TLC analysis to establish completion. After cooling to room temperature, the reaction was diluted with ethyl acetate (30 mL), washed with water (30 mL) and brine (30 mL). The organic phase was dried (anhydrous MgSO4) and concentrated under reduced pressure. The residue was purified by column chromatography (Silica Gel, petroleum ether/ethyl acetate).
methyl 2-(5,5,6,6,7,7,8,8,8-nonafluorooct-1-yn-1-yl)benzoate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
100 mg
With copper(l) iodide; bis(eta3-allyl-mu-chloropalladium(II)); 1,3-di(adamantan-1-yl)-1H-imidazol-3-ium chloride; caesium carbonate; In diethyl ether; N,N-dimethyl-formamide; at 40℃; for 24h;
Allyl palladium chloride dimer (9.20 mg, 25 mumol),1,3-di-1-adamantyl imidazolium chloride (IAd HCl)(19.8 mg, 50 mumol), copper iodide (21.6 mg, 112 mumol)And cesium carbonate (228 mg, 0.70 mmol) in dimethylformamide-diethyl ether mixed solvent (1: 2) (1 mL).Methyl 2-ethynyl benzoate (30) (52 muL, 0.375 mmol)And 2- (nonafluorobutyl) ethyl iodide (27a) (86 muL, 0.500 mmol) were added, and the mixture was stirred at 40 C. for 24 hours.After filtration, the reaction solution was concentrated under reduced pressure,Purification by silica gel column chromatography (dichloromethane: hexane = 1:30 to 1: 8)Methyl 2- (5,5,6,6,7,7,8,8,8-nonafluorooct-1-yn-1-yl) benzoate (31a)(100 mg, 0.250 mmol, 50% from 27a, 67% from 30)Was obtained as a yellow oil.
methyl 2-(5,5,6,6,7,7,8,8,9,9,10,10,10-tridecafluorodec-1-yn-1-yl)benzoate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
629 mg
With copper(l) iodide; bis(eta3-allyl-mu-chloropalladium(II)); 1,3-di(adamantan-1-yl)-1H-imidazol-3-ium chloride; caesium carbonate; In diethyl ether; N,N-dimethyl-formamide; at 40℃; for 24h;
Allyl palladium chloride dimer (46 mg, 0.13 mmol),1,3-di-1-adamantyl imidazolium chloride (IAd HCl)(99 mg, 0.25 mmol), copper iodide (108 mg, 0.56 mmol)And cesium carbonate (1.14 g, 3.5 mmol) in N, N-dimethylformamide-diethyl ether (1: 2) (5 mL)Methyl 2-ethynyl benzoate (30) (0.46 mL, 1.88 mmol)And 1H, 1H, 2H, 2H-tridecafluoro-n-octyl iodide (27b) (0.60 mL, 2.5 mmol) were added, and the mixture was stirred at 40 C. for 24 hours.After filtration, the reaction solution was concentrated under reduced pressure,Purification by silica gel column chromatography (dichloromethane: hexane = 1:30 to 1: 8)Methyl 2- (5,5,6,6,7,7,8,8,9,9,10,10,10-tridecafluorodec-1-yn-1-yl) benzoate (31b)(629 mg, 1.24 mmol, 50% from 27b, 66% from 30)Was obtained as a yellow oil.
With palladium on activated charcoal; triethylamine; triphenylphosphine; zinc(II) chloride; In N,N-dimethyl-formamide; at 110℃; for 12h;Inert atmosphere;
Into a 50-mL round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed 7.1 (300 mg, 0.574 mmol, 1 equiv), methyl 2- ethynylbenzoate (110.26 mg, 0.688 mmol, 1.2 equiv), PPI13 (37.62 mg, 0.143 mmol, 0.25 equiv), Pd/C (3 mg, 0.028 mmol, 0.05 equiv), ZnCk (7.82 mg, 0.057 mmol, 0.1 equiv), Et3N (406.34 mg, 4.016 mmol, 7 equiv), DMF (7.5 mL). The resulting solution was stirred for 12 h at 110 C in an oil bath. The solids were filtered out. The resulting solution was extracted with 3x10 mL of ethyl acetate. The resulting mixture was washed with 1 x10 mL of brine. The mixture was dried over anhydrous sodium sulfate and concentrated. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1 :2). This resulted in 60 mg (19%) of 7.2 as white solid. LC-MS (ES, m/z): [M+H]+ 553.8.
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