* 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 tungstate sulfuric acid In neat (no solvent) at 80 - 90℃; for 0.0666667 h;
General procedure: To a mixture of orthoester (1.1 mmol) and o-aminophenol or o-aminothiophenol (1 mmol) was added TSA (1 molpercent). The mixture was stirred at 80–90 °C for the appropriate time according to Table 4. After the completion of the reaction (as indicated by TLC), the mixture was diluted with chloroform (10 mL) and the catalyst was separated by filtration. Further purification was achieved by column chromatography
83%
for 4 h; Reflux
General procedure: A mixture of 2-aminophenol derivative (5 mmol) and triethyl orthoformate (15 mL) was heated at reflux for 4 h. After cooling to room temperature, remained triethyl orthoformate was removed under reduced pressure and the residue was purified by column chromatography on silica gel.
77%
at 150℃; for 8 h; Inert atmosphere
General procedure: A solution of substituted 2-aminophenol (20 mmol) in triethyl orthoformate (30 mL) was heated to 150°C for 8 h under argon. The mixture was cooled to room temperature and the triethyl orthoformate was removed by distillation under reduced pressure. The resulting residue was purified by silica gel column chromatography to afford substituted benzoxazole.
Reference：
[1] Comptes Rendus Chimie, 2013, vol. 16, # 11, p. 1029 - 1034
[2] Combinatorial Chemistry and High Throughput Screening, 2013, vol. 16, # 8, p. 618 - 627
[3] Monatshefte fur Chemie, 2007, vol. 138, # 7, p. 663 - 667
[4] Angewandte Chemie - International Edition, 2012, vol. 51, # 19, p. 4666 - 4670
[5] Monatshefte fur Chemie, 2011, vol. 142, # 1, p. 87 - 91
[6] Chemical Communications, 2014, vol. 50, # 73, p. 10661 - 10664
[7] Organic Preparations and Procedures International, 2013, vol. 45, # 1, p. 57 - 65
[8] Organic Letters, 2011, vol. 13, # 3, p. 522 - 525
[9] Tetrahedron Letters, 2012, vol. 53, # 34, p. 4588 - 4590
[10] Angewandte Chemie - International Edition, 2011, vol. 50, # 48, p. 11511 - 11515
[11] Chemical Communications, 2015, vol. 51, # 81, p. 15059 - 15062
[12] Tetrahedron Letters, 2015, vol. 56, # 3, p. 511 - 513
[13] Journal of Organic Chemistry, 2011, vol. 76, # 13, p. 5444 - 5449
[14] Organic and Biomolecular Chemistry, 2012, vol. 10, # 18, p. 3715 - 3720
[15] Organic Letters, 2010, vol. 12, # 15, p. 3567 - 3569
[16] Journal of Molecular Catalysis A: Chemical, 2010, vol. 328, # 1-2, p. 119 - 123
[17] Chemical Communications, 2011, vol. 47, # 41, p. 11522 - 11524
[18] Chemical Communications, 2012, vol. 48, # 42, p. 5181 - 5183
[19] Angewandte Chemie - International Edition, 2012, vol. 51, # 28, p. 6993 - 6997
[20] Angewandte Chemie - International Edition, 2013, vol. 52, # 16, p. 4457 - 4461[21] Angew. Chem., 2013, vol. 125, # 16, p. 4553 - 4557,5
[22] Journal of Organic Chemistry, 2016, vol. 81, # 23, p. 11743 - 11750
[23] Tetrahedron Letters, 2019, vol. 60, # 1, p. 68 - 71
3
[ 95-85-2 ]
[ 149-73-5 ]
[ 17200-29-2 ]
Yield
Reaction Conditions
Operation in experiment
95%
With sodium sulfate In tetrahydrofuran at 55 - 60℃; Inert atmosphere
2-amino-4-chloro phenol (50 g, 0.349 moles), Trimethyl orthoformate (111 g, 1.048 moles), sodium sulphate (9.93 g, 0.069 moles) and THF (500 mL) were charged in round bottom flask at room temperature (RT) under inert atmosphere. Reaction mass was heated to 55° C. to 60° C. The progress of the reaction was monitored by TLC. After completion of the reaction, reaction mixture was cooled to room temperature and quenched with water (50 ml). Reaction mass was cooled to RT, diluted with water (250 ml) and extracted with ethyl acetate (2*250 ml). The combined organic extracts were dried over sodium sulphate, filtered and concentrated under reduced pressure. The obtained crude material was purified by column chromatography using silica gel (60-120 mesh) eluted with 20percent EtOAc-hexane to give 5-Chloro-1,3-benzoxazole (Formula XI, 50 g, yield 95percent, HPLC purity of 99.46percent) as a yellow color solid.
Reference：
[1] Patent: US2016/168138, 2016, A1, . Location in patent: Paragraph 0118-0119
[2] Combinatorial Chemistry and High Throughput Screening, 2013, vol. 16, # 8, p. 618 - 627
[3] Journal of Chemical Sciences, 2014, vol. 126, # 3, p. 579 - 585
[4] Monatshefte fur Chemie, 2011, vol. 142, # 1, p. 87 - 91
[5] Journal of Molecular Catalysis A: Chemical, 2010, vol. 328, # 1-2, p. 119 - 123
[6] Organic Letters, 2012, vol. 14, # 13, p. 3458 - 3461
[7] Patent: WO2012/148553, 2012, A1, . Location in patent: Page/Page column 39-40
[8] Patent: US9441254, 2016, B2, . Location in patent: Paragraph 10; 11
4
[ 61-80-3 ]
[ 17200-29-2 ]
Reference：
[1] Chemical and Pharmaceutical Bulletin, 1997, vol. 45, # 9, p. 1547 - 1549
5
[ 123-39-7 ]
[ 95-85-2 ]
[ 17200-29-2 ]
Reference：
[1] Journal of Pharmaceutical Sciences, 1964, vol. 53, p. 538 - 544
6
[ 124-38-9 ]
[ 74-88-4 ]
[ 17200-29-2 ]
[ 27383-92-2 ]
Yield
Reaction Conditions
Operation in experiment
82%
Stage #1: With 3-benzyl-1-(1-((2,6-diisopropylphenyl)imino)ethyl)-1H-imidazol-3-ium chloride; potassium <i>tert</i>-butylate In N,N-dimethyl-formamide at 80℃; for 18 h; Inert atmosphere Stage #2: at 65℃; for 1 h; Inert atmosphere
In the reaction flask, Under argon, a catalyst (9.9 mg, 0.025 mmol, 5 molpercent), potassium tert-butoxide (0.0672 g, 0.6 mmol) DMF (3.0 ml), 5-chlorobenzoxazole (76.79 mg, 0.5 mmol) was added to the carbon dioxide gas, and the reaction was stirred at 80 ° C for 18 hours under normal pressure. Cooled to 65 ° C, methyl iodide (93 μl, 1.5 mmol) was added, The reaction was stirred at 65 ° C for 1 hour. Cooled to room temperature, the reaction was terminated with deionized water, The reaction product was extracted with ethyl acetate and purified by column chromatography (Using a mixed solvent of ethyl acetate / petroleum ether in a volume ratio of 1:10 as a developing solvent) The yield was 82percent.
Reference：
[1] Organic Letters, 2010, vol. 12, # 15, p. 3567 - 3569
[2] Green Chemistry, 2018, vol. 20, # 5, p. 989 - 996
[3] Patent: CN106565623, 2017, A, . Location in patent: Paragraph 0038
[4] Green Chemistry, 2013, vol. 15, # 3, p. 635 - 640
7
[ 17200-29-2 ]
[ 27383-92-2 ]
Reference：
[1] Organic Letters, 2012, vol. 14, # 15, p. 3986 - 3989
[2] Green Chemistry, 2016, vol. 18, # 13, p. 3804 - 3807
8
[ 17200-29-2 ]
[ 22876-19-3 ]
Yield
Reaction Conditions
Operation in experiment
73.7%
With 1.3-propanedithiol; potassium hydroxide In dimethyl sulfoxide at 130℃; for 12 h; Inert atmosphere; Sealed tube
153.57 mg (1 mmol) of 5-chlorobenzoxazole, 216 μL (2.0 mmol) of 1,3-propanedithiol, 280.55 mg (5.0 mmol) of potassium hydroxide and 3 mL of DMSO were placed in a reaction equipped with a magnetic stir bar. The tube was sealed with argon, heated and stirred, and reacted in an oil bath at 130 ° C for 24 hours. After the reaction is completed, the reaction solution is transferred to a separating funnel with water washing, an appropriate amount of dilute hydrochloric acid is added, the aqueous phase is adjusted to pH 1-3, and the organic phase is extracted with ethyl acetate, and the upper organic phase is transferred with anhydrous magnesium sulfate. The mixture was dried under reduced pressure and purified by column chromatography to yield 113.2mg of product as a red-brown solid, yield 73.7percent.
Reference：
[1] Patent: CN108530374, 2018, A, . Location in patent: Paragraph 0030; 0031
[2] Organic and Biomolecular Chemistry, 2017, vol. 15, # 39, p. 8276 - 8279
9
[ 17200-29-2 ]
[ 13589-72-5 ]
Reference：
[1] Journal of the American Chemical Society, 2004, vol. 126, # 26, p. 8197 - 8205
With potassium acetate;palladium diacetate; In tetrahydrofuran; at 80℃;
A mixture of 5-chlorobenzoxazole (0.129 g, 0.84 mmol), 4,4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi-1,3,2-dioxaborolane (0.4956 g, 1.95 mmol), potassium acetate (0.41 g, 4.2 mmol), 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene hydrochloride (43 mg, 0.10 mmol) and palladium acetate (11 mg, 0.05 mmol) was degassed, treated with tetrahydrofuran (10 mL) and the resulting mixture heated at 80 C. overnight. The mixture was diluted with water (100 mL), acidified to pH 6 and extracted with EtOAc (3×40 mL). The extracts were washed with water, dried and concentrated in vacuo. The residue so obtained was purified by chromatography over silica gel eluting with DCM to 10% MeCN/DCM to afford 1,3-benzoxazole-5-boronic acid, pinacol ester. 1H NMR (400 MHz, CHLOROFORM-d) delta ppm 1.37-1.39 (m, 12H) 7.59 (d, J=8.34 Hz, 1H) 7.86 (dd, J=8.08, 1.01 Hz, 1H) 8.10 (s, 1H) 8.26 (s, 1H); MS (ES+): m/z 246.23 [MH+].
With potassium acetate;palladium diacetate; In tetrahydrofuran; at 80℃;
A mixture of 5-chlorobenzoxazole (0.129 g, 0.84 mmol), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi-1,3,2-dioxaborolane (0.4956 g, 1.95 mmol), potassium acetate (0.41 g, 4.2 mmol), 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene hydrochloride (43 mg, 0.10 mmol) and palladium acetate (11 mg, 0.05 mmol) was degassed, treated with tetrahydrofuran (10 mL) and the resulting mixture heated at 80 C. overnight. The mixture was diluted with water (100 mL), acidified to pH 6 and extracted with EtOAc (3×40 mL). The extracts were washed with water, dried and concentrated in vacuo. The residue so obtained was purified by chromatography over silica gel eluting with DCM to 10% MeCN/DCM to afford 1,3-benzoxazole-5-boronic acid, pinacol ester. 1H NMR (400 MHz, CHLOROFORM-d) delta ppm 1.37-1.39 (m, 12 H) 7.59 (d, J=8.34 Hz, 1 H) 7.86 (dd, J=8.08, 1.01 Hz, 1 H) 8.10 (s, 1 H) 8.26 (s, 1 H); MS (ES+): m/z 246.23 [MH+]. This material was used in place of 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole under the conditions described in example 1 to afford 1-(1,3-benzoxazol-5-yl)-3-cyclobutylimidazo[1,5-a]pyrazin-8-amine MS (ES+): m/z 306.16 [MH+].
With hydridotetakis(triphenylphosphine)rhodium(I); 1,2-bis-(diphenylphosphino)ethane In chlorobenzene for 6h; Inert atmosphere; Reflux;
Typical Procedures for Phenylthiolation Reaction. 2-Phenylthio-1,3-benzothiazole 710
General procedure: In a two-necked flask equipped with a reflux condenser were placed RhH(PPh3)4 (4 mol%, 11.5 mg), 1,2-bis(diphenylphosphino)ethane (8 mol%, 8.0 mg), 1,3-benzothiazole 5 (0.25 mmol, 27.3 mL), and (α-phenylthio)isobutyrophenone 6 (0.25 mmol, 64.0 mg) in chlorobenzene (0.25 mL) under an argon atmosphere, and the solution was heated at reflux for 3 h. The mixture was purified by flash column chromatography on silica gel giving 7 (55.8 mg, 92%) and isobutyrophenone 8 (34.3 mg, 93%) with the recovery of 5 (3.5 mg, 10%) and 6 (0.8 mg, 1%).
With silver hexafluoroantimonate; dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; oxygen; silver carbonate; Trimethylacetic acid; In 1,2-dichloro-benzene; at 140℃; for 24h;Schlenk technique; Sealed tube;
General procedure: A 25 mL flame-dried Schlenk tube was charged with the1-(pyrimid-2-yl)-1H-indoles 1 (0.25 mmol), 1,3-azoles2 (0.75 mmol), [RhCp*Cl2]2 (3.9 mg, 2.5 mol%), AgSbF6(8.6 mg, 10 mol%), pivalic acid (PivOH,51 mg, 0.50 mmol), Ag2CO3 (6.9 mg, 10 mol%), and DCB(1.0 mL). The tube was sealed under an O2 atmosphere.The reaction mixture was stirred vigorously and heated at140 C for 24 h, and then cooled to ambient temperature.The final reaction mixture was diluted with 10-20 mL ofCH2Cl2, filtered through a Celite pad to remove insolublesalts, and then washed with 10-20 mL of CH2Cl2. Thecombined CH2Cl2 extracts were concentrated in a vacuumevaporator and the crude product was purified by flashcolumn chromatography on silica gel (petroleum ether/ethylacetate=3/1, v/v) to give the desired product 3 or 4.
With 1,3-bis-(diphenylphosphino)propane; palladium dichloride; silver(l) oxide In benzene at 60℃; for 12h; Inert atmosphere;
51%
With 1,3-bis-(diphenylphosphino)propane; palladium dichloride; silver(l) oxide In benzene at 60℃; for 12h;
11 [Example 11] Preparation of [5-chloro-2-(hept-1-ynyl)benzoxazole]
In a V- vial PdCl2 (6.7 mg, 0.03 mmol), dppp (24.7 mg, 0.06 mmol), Ag2O (208.6 mg, 0.9 mmol), octynoic acid(63.1 mg, 0.45 mmol), 5-chlorobenzoxazole(46.1 mg, 0.3 mmol) and then benzene (1.8 mL) was added and the reaction was terminated after stirring for 12 hours at 60°C. The temperature of the V- vial was lowered to room temperature, and then extracted with Et2O (3 x 20mL) and washed with saturated aqueous solution of NH4Cl (20 mL). The organic layer was extracted, dried over anhydrous MgSO4 and filtered. After removing the solvent by separation by column chromatography, to give the title compound 5-chloro-2-(hept-1-ynyl)benzoxazole (37.9 mg, 51%).
With palladium diacetate; sodium t-butanolate; nixantphos In N,N-dimethyl-formamide at 24℃; for 12h; Inert atmosphere;
73%
With copper(II) oxide; potassium carbonate; triphenylphosphine In diethylene glycol dimethyl ether at 160℃; for 5h; Reflux; Inert atmosphere; Sealed tube;
5.1
General procedure: 4.3 General procedure for CuO-catalyzed arylation and alkenylation of 1,3-azole (0012) Under argon, 0.5mmol of the bromobenzene or bromoalkene was added to the reaction mixture containing 0.25mmol of the benzoxazole, 0.5mmol K2CO3, 0.025mmol CuO, and 0.075mmol PPh3, followed by the addition of 2mL dry diglyme. The sealed reaction tube was stirred at 160°C for 5-24h. After cooling, the reaction mixture was centrifuged to remove solid and separated the organic phase. Then, organic phase was extracted and dried over anhydrous MgSO4, and concentrated under reduced pressure after filtered. The residue was purified by column chromatography on silica gel eluted to afford corresponding product.
With tert.-butylhydroperoxide; tetra-(n-butyl)ammonium iodide; acetic acid In water; acetonitrile at 100℃; for 0.333333h; Microwave irradiation; Green chemistry;
4.2 General procedure for the synthesisof benzoxazol-2-amine derivatives
General procedure: Benzoxazole 1 (0.25 mmol), tertiary amines 2 (0.75 mmol),TBAI (0.025 mmol, 10 mg), TBHP (70 % aqueous solution,0.5 mmol), and AcOH (0.5 mmol, 30 mg) in CH3CN(1.5 mL) were added to a 5-mL microwave reaction tube.The reaction mixture was put into a microwave reactor at100 °C for 20 min. After completion of the reaction, themixture was quenched by addition of a saturated solutionof sodium disulfite (1.0 mL) and a saturated solutionof sodium hydrogen carbonate (2.0 mL). Then the mixturewas extracted with ethyl acetate (3 × 5 mL), combinedorganic phases were dried over anhydrous Na2SO4, andthe organic solvent was removed under vacuum. Thecrude residue was purified by chromatography on a silicagel column using ethyl acetate-petroleum ether (1:5 to 2:1)as eluant to obtain the desired product.
5-chloro-2-((4-methoxyphenyl)ethynyl)benzoxazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
73%
With 1,3-bis-(diphenylphosphino)propane; palladium dichloride; silver(l) oxide In benzene at 60℃; for 12h;
12 [Example 12] Preparation of [5-chloro-2-((4-methoxyphenyl)ethynyl)benzoxazole]
In a V- vial PdCl2 (6.7 mg, 0.03 mmol), dppp (24.7 mg, 0.06 mmol), Ag2O (208.6 mg, 0.9 mmol), 3- (4-methoxyphenyl) propiolic acid(79.3 mg, 0.45 mmol), 5-chlorobenzoxazole(46.1 mg, 0.3 mmol) and then benzene (1.8 mL) was added and the reaction was terminated after stirring for 12 hours at 60°C. The temperature of the V- vial was lowered to room temperature, and then extracted with Et2O (3 x 20mL) and washed with saturated aqueous solution of NH4Cl (20 mL). The organic layer was extracted, dried over anhydrous MgSO4 and filtered. After removing the solvent by separation by column chromatography, to give the title compound 5-chloro-2-((4-methoxyphenyl)ethynyl)benzoxazole (62.1 mg, 73%).
With 1,3-bis-(diphenylphosphino)propane; palladium dichloride; silver(l) oxide; In benzene; at 60℃; for 12h;
In a V- vial PdCl2 (6.7 mg, 0.03 mmol), dppp (24.7 mg, 0.06 mmol), Ag2O (208.6 mg, 0.9 mmol), 3-methyl-tolyl-propiolic acid(72.1 mg, 0.45 mmol), 5-chlorobenzoxazole(46.1 mg, 0.3 mmol) and then benzene (1.8 mL) was added and the reaction was terminated after stirring for 12 hours at 60C. The temperature of the V- vial was lowered to room temperature, and then extracted with Et2O (3 x 20mL) and washed with saturated aqueous solution of NH4Cl (20 mL). The organic layer was extracted, dried over anhydrous MgSO4 and filtered. After removing the solvent by separation by column chromatography, to give the title compound 5-chloro-2-(m-tolylethynyl)benzoxazole (23.3 mg, 29%).
With tert.-butylhydroperoxide; 1-(n-butyl)pyridinium iodide; acetic acid In water; acetonitrile at 20℃; for 3.5h; Green chemistry;
II. General experimental procedure
General procedure: A reaction vessel was charged with acetic acid (2.016 mmol) and TBHP (70% inwater, 1.008 mmol) in acetonitrile (2 mL). After the addition of [Bpy]I (0.1008 mmol),benzoxazole (0.672 mmol) and secondary amines (1.344 mmol) were added. Then thereaction mixture was stirred at room temperature for 3.5 hours. After the reactionfinished, the mixture was extracted with dichloromethane (5 × 10 mL), and thecombined organic phases were dried over anhydrous Na2SO4. The solvent wasevaporated under vacuo, and the crude residue was purified by columnchromatography on silica gel. Aqueous phase was dried in a vacuum evaporator torecover the ionic liquid and directly reused in subsequent runs.
5-chloro-2-(2-methylprop-1-en-1-yl)benzo[d]oxazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
78%
With copper(l) chloride; lithium tert-butoxide In toluene at 110℃; for 1h; Inert atmosphere;
78%
With copper(l) chloride; lithium tert-butoxide In toluene at 110℃; for 2h;
3 Synthesis of 5-chloro-2- (2-methyl-1-propenyl) benzoxazole
154 mg (ie 1 mmol) of 5-chlorobenzoxazole, 203 mg (ie 1.5 mmol) of 2-methyl-3-bromopropene, 240 mg (ie 3 mmol) of lithium tert-butoxide and 8 mg 0.08 mmol) cuprous chloride, and then add 2mL toluene, stirred at 110oC for 2 hours, the reaction was concentrated to petroleum ether: ethyl acetate, the volume ratio of 250: 1 as eluant by silica gel column chromatography to obtain5-chloro-2- (2-methyl-1-propenyl) benzoxazole, which structural formula is as follows:The compound is a yellow solid with a yield of 78% and its nuclear magnetic data is as follows:
With 1.3-propanedithiol; potassium hydroxide; In dimethyl sulfoxide; at 130℃; for 12h;Inert atmosphere; Sealed tube;
153.57 mg (1 mmol) of 5-chlorobenzoxazole, 216 muL (2.0 mmol) of 1,3-propanedithiol, 280.55 mg (5.0 mmol) of potassium hydroxide and 3 mL of DMSO were placed in a reaction equipped with a magnetic stir bar. The tube was sealed with argon, heated and stirred, and reacted in an oil bath at 130 C for 24 hours. After the reaction is completed, the reaction solution is transferred to a separating funnel with water washing, an appropriate amount of dilute hydrochloric acid is added, the aqueous phase is adjusted to pH 1-3, and the organic phase is extracted with ethyl acetate, and the upper organic phase is transferred with anhydrous magnesium sulfate. The mixture was dried under reduced pressure and purified by column chromatography to yield 113.2mg of product as a red-brown solid, yield 73.7%.
69%
With 1.3-propanedithiol; dimethyl sulfoxide; potassium hydroxide; at 130℃; for 12h;Inert atmosphere;
General procedure: To a solution of benzothiazoles or benzoxazoles (1, 1 mmol) in DMSO (3 mL), was added KOH (280 mg, 5 equiv) and 1,3-propanedithiol (207 muL, 2 mmol). The reaction mixture was heated under argon at 130 C for 12 h. After cooling to room temperature, water (10 mL) was added. The pH of the reaction mixture was adjusted to 3-4 using 5% HCl. The resulting mixture was extracted with ethyl acetate (15 mL ×2). The organic layer was washed with water and brine, dried over anhydrous MgSO4 and concentrated using rotary evaporator. The crude product was purified by silica gel column chromatography using ethyl acetate/n-hexane as eluent to afford the corresponding heteroaryl thiols 3.
With tris-(dibenzylideneacetone)dipalladium(0); sodium t-butanolate; nixantphos In tetrahydrofuran at 25℃; for 24h; Glovebox; Inert atmosphere;
2. A typical procedure for the Pd-catalyzed alkenylation of azole heterocycles
General procedure: An oven-dried 10 mL reaction vial equipped with a stir bar was charged with azole heterocycles (1, 0.2 mmol, 1.0 equiv) and alkenyl bromides (2, 0.30 mmol, 1.5 equiv) in a glove box under a nitrogen atmosphere. A solution of catalytic Pd2(dba)3 (9.15 mg, 0.01 mmol, 5 mol%) and NiXantphos (11.03 mg, 0.02 mmol, 10 mol%) was stirred in 1 mL of dry tetrahydrofuran (THF) for 2 h at room temperature. Then, t-BuONa (57.7 mg, 0.6 mmol, 3.0 equiv) and reagent mixed with catalyst were added to the reaction mixture. And thenthe vial was capped. According to the temperature requirements for different products, some vials were stirred in the glove box for 24 h, but others were removed from the glove box, and stirred for 24 h at 70 or 150 . The reaction mixture was quenched with three drops of H2O, diluted with 3 mL of ethyl acetate, and filtered over a pad of silica. The pad was rinsed with ethyl acetate (15-25 mL), and the combined solutions were concentrated in vacuo. The crude material was loaded onto a deactivated silica gel column and purified by flash chromatography to afford the desired product.
2-[adamantan-1-yl]-5-chlorobenzo[d]oxazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
90%
With [Co(dyimethylglyoximate(1-))2(pyridine)2]PF6; tetrabutylammonium acetate In ethyl acetate at 40 - 44℃; for 30h; Irradiation; Schlenk technique; Inert atmosphere;
59%
With dipotassium hydrogenphosphate; dichloro(dimethylglyoxime)(dimethylglyoximato)cobalt(III); 9-(2-mesityl)-10-methylacridinium perchlorate In water; 1,2-dichloro-ethane at 25 - 30℃; for 24h; Inert atmosphere; Irradiation; Schlenk technique;
Visible-Light-Promoted Decarboxylative C-H Adamantylation;General Procedure
General procedure: To an oven-dried 10 mL vial were added the heteroarene 1 (0.40 mmol, 1.0 equiv), 1-adamantanecarboxylic acid (2; 216 mg, 1.20 mmol, 3.0 equiv), K2HPO4 (209 mg, 1.20 mmol, 3.0 equiv), 9-mesityl-10-methylacridinium perchlorate (8.2 mg, 5.0 mol%), and [Co(dmgH)(dmgH2)Cl2] (11.6 mg, 8.0 mol%). After the vial was capped with a septum, it was evacuated and refilled with N2 for three times before DCE (1.5 mL) and H2O (0.5 mL) were added sequentially. If the heterocyclic substrate 1 was a liquid, it was added at this point. The mixture was degassed and stirred for 24 h under visible light irradiation (Kessil A360N, see Figure S-1 in the Supporting Information). After 24 h, the mixture was diluted with CH2Cl2 (10 mL) and H2O (10 mL), and the phases were separated. The aqueous layer was extracted with CH2Cl2 (2 × 10 mL), the combined organic phases were dried (Na2SO4), and the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel (n-pentane or n-hexane/Et2O 20:1 to 2:1) affording the corresponding product 3.
With copper(l) iodide; potassium phosphate tribasic heptahydrate; palladium diacetate; nixantphos In N,N-dimethyl-formamide at 120℃; for 12h; Inert atmosphere;
2. General procedure for direct 2-arylation of benzoxazoles with aryl chlorides
General procedure: 2 mol% Pd(OAc)2/3 mol% Nixantphos, anhydrous DMF (1.0 ml) were added to an oven-dried 10 ml reaction vial equipped with a stir bar, the mixture was stirred at 45 °C under an argon atmosphere for 1h to be a dark brown solution. 1 mol% CuI/1.1 mol% Nixantphos, anhydrous DMF (1.0 ml) were added to an oven-dried 10 ml reaction vial equipped with a stir bar, the mixture was stirred at 60 °C under an argon atmosphere for 2h to be a colorless transparent solution. The amount of catalyst and solvent should scaled up by the number of reactions. Benzoxazoles (0.25 mmol), aryl chlorides (0.3 mmol) and K3PO4*7H2O (42.3 mg, 0.125 mmol, 0.5 equiv) were added to an oven-dried 10 ml reaction vial equipped with a stir bar. A stock solution of Pd(OAc)2/Nixantphos and CuI/Nixantphos in 1 ml of dry DMF was taken up by syringe and added to the reaction vial. The reaction vial filled with argon was then sealed with a septum. The reaction mixture was stirred for12 h or 24 h at 120 °C, quenched with two drops of H2O, diluted with 3 mL of ethyl acetate, and filtered over a pad of MgSO4 and silica. The pad was rinsed with additional ethyl acetate, and the solution was concentrated in vacuo. The crude material was loaded onto a silica gel column and purified by flash chromatography.
5-chloro-2-(thiophen-3-yl)benzo[d]oxazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
65%
With copper(l) iodide; potassium phosphate tribasic heptahydrate; palladium diacetate; nixantphos; In N,N-dimethyl-formamide; at 120℃; for 12h;Inert atmosphere;
General procedure: 2 mol% Pd(OAc)2/3 mol% Nixantphos, anhydrous DMF (1.0 ml) were added to an oven-dried 10 ml reaction vial equipped with a stir bar, the mixture was stirred at 45 C under an argon atmosphere for 1h to be a dark brown solution. 1 mol% CuI/1.1 mol% Nixantphos, anhydrous DMF (1.0 ml) were added to an oven-dried 10 ml reaction vial equipped with a stir bar, the mixture was stirred at 60 C under an argon atmosphere for 2h to be a colorless transparent solution. The amount of catalyst and solvent should scaled up by the number of reactions. Benzoxazoles (0.25 mmol), aryl chlorides (0.3 mmol) and K3PO4*7H2O (42.3 mg, 0.125 mmol, 0.5 equiv) were added to an oven-dried 10 ml reaction vial equipped with a stir bar. A stock solution of Pd(OAc)2/Nixantphos and CuI/Nixantphos in 1 ml of dry DMF was taken up by syringe and added to the reaction vial. The reaction vial filled with argon was then sealed with a septum. The reaction mixture was stirred for12 h or 24 h at 120 C, quenched with two drops of H2O, diluted with 3 mL of ethyl acetate, and filtered over a pad of MgSO4 and silica. The pad was rinsed with additional ethyl acetate, and the solution was concentrated in vacuo. The crude material was loaded onto a silica gel column and purified by flash chromatography.
With manganese; 4,4'-Dimethoxy-2,2'-bipyridin; magnesium chloride; nickel dibromide; In 1-methyl-pyrrolidin-2-one; at 80℃; for 24h;Inert atmosphere; Sealed tube;
Under a nitrogen atmosphere, nickel bromide (4.4 mg, 0.02 mmol),4,4'-dimethoxy-2,2'-bipyridine (4.3 mg, 0.02 mmol), magnesium chloride (28.6 mg, 0.3 mmol), manganese powder (43.95 mg, 0.8 mmol), and a solvent NMP (0.5 mL) was added )And stir well. Weigh 5-chlorobenzoxazole (30.71 mg, 0.2 mmol) and dissolve it in NMP (0.5 mL). After dissolution, add <strong>[762-51-6]1-fluoro-2-iodoethane</strong> (26 muL, 0.3 mmol).And mix well, the solution is transferred to the sealed tube. After sealing, stir the reaction in an oil bath at 80 C for 24 hours, cool the reaction solution to room temperature, add an equal volume of saturated ammonium chloride solution to the reaction solution diluted with ether (5mL), filter through a diatomaceous earth funnel, and rinse with a small amount of ether Collect the filtrate.The filtrate was extracted three times with diethyl ether, and the organic phases were combined (add internal standard dodecane,GC-MS determined crude yield). Dry over anhydrous sodium sulfate, filter, and remove the solvent by distillation under reduced pressure.After the residue was separated by silica gel column chromatography, the product was weighed, and the calculated yield was 70%.
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