* 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] Journal of the Brazilian Chemical Society, 2011, vol. 22, # 11, p. 2036 - 2039
2
[ 332883-48-4 ]
[ 84459-32-5 ]
Yield
Reaction Conditions
Operation in experiment
78%
With potassium phosphate; copper(l) iodide; 1,10-Phenanthroline In 1,4-dioxane at 80℃; Schlenk technique
General procedure: In an oven dried Schlenk tube, were added alcohol 1 (69.0–199.5 mg, 0.5 mmol), CuI (10 molpercent)and 1,10-Phenanthroline (20 molpercent) and K3PO4 (2 mmol) followed by the addition of dioxane (2mL) at room temperature under open air atmosphere. The stirred reaction mixture was heated inan oil bath at 80 C for 7–48 h. Progress of the reaction was monitored by TLC till the reaction iscompleted. Then, the reaction mixture was cooled to room temperature, quenched with aqueousNH4Cl solution and then extracted with CH2Cl2 (3 10 mL). The organic layer was washed withsaturated NaCl solution, dried (Na2SO4), and filtered. Evaporation of the solvent under reducedpressure and purification of the crude material by silica gel column chromatography (petroleumether/ethyl acetate) furnished the aldehyde/ketone 2 (61–97percent).
Reference:
[1] Journal of the American Chemical Society, 2009, vol. 131, p. 54 - 55
[2] Synthetic Communications, 2014, vol. 44, # 14, p. 2076 - 2087
[3] Patent: US6514964, 2003, B1,
[4] Journal of the American Chemical Society, 2011, vol. 133, # 20, p. 7916 - 7925
3
[ 6630-33-7 ]
[ 84459-32-5 ]
Yield
Reaction Conditions
Operation in experiment
94%
at 0℃; for 4.66667 h;
To a solution of 2-bromobenzaldehyde (10.0 g, 53.7 mmol) in H2SO4 (100 mL) was added K O3 (5.43 g, 53.7 mmol) in portions over 1 h at 0°C. The mixture was stirred for 40 min and additional K O3 (0.72 g) was added. The reaction mixture was stirred at 0°C for 3 h then poured into ice water. The resulting precipitate was collected by filtration, rinsed with water and recrystallized from EtOAc/Pentane to give 2-bromo-5-nitrobenzaldehyde (11.7 g, 94percent yield) as a white solid. MS (ESI) calcd for C7H4BrN03: 228.9
94%
at 0℃; for 3.67 h;
To a solution of 2-bromobenzaldehyde (10.0 g, 53.7 mmol) in H2SO4 (100 mL) was added KNO3 (5.43 g, 53.7 mmol) in portions over 1 h at 0° C. The mixture was stirred for 40 min and additional KNO3 (0.72 g) was added. The reaction mixture was stirred at 0° C. for 3 h then poured into ice water. The resulting precipitate was collected by filtration, rinsed with water and recrystallized from EtOAc/Pentane to give 2-bromo-5-nitrobenzaldehyde (11.7 g, 94percent yield) as a white solid. MS (ESI) calcd for C7H4BrNO3: 228.9.
83%
at 0℃; for 3 h;
KNO3 (1.09 g, 10.8 mmol) was added slowly to a stirred red solution of 2-bromobenzaldehyde (2.0 g, 10.8 mmol) in H2SO4 (10 mL) at 0 °C. After 30 minutes extra portion of KNO3 (0.16 g, 1.6 mmol) was added, and the reaction mixture was stirred for 2.5 hours at 0 °C. Then the reaction mixture was poured over ice water (50 mL), extracted with Et2O (3×25 mL). Combined organic layers were washed with water (30 mL), brine (40 mL) and dried over Na2SO4. Solvents were evaporated in vacuo. The residual yellow solid was recrystallized from EtOAc/hexane (1/2, 40 mL) to give pure nitroaldehyde SI-1e (1.32 g, 5.7 mmol, 53percent). Further recrystallization of evaporated mother liquor from EtOAc/hexane (1/3, 15 mL) gives additional nitroaldehyde SI-1e (0.75 g, 3.2 mmol, 30percent) of the same purity.
55%
at 5 - 20℃; for 1.5 h;
A mixture of concentrated sulfuric acid (17.01 mL) andfuming nitric acid (2.250 mL) was cooled to 5 °C followedby the dropwise addition of 2—bromobenzaldehyde (3.15 mL,27.0 mmol) over a period of 30 minutes. The mixture wasthen allowed to warm to room temperature and stirred for60 minutes. The reaction mixture was poured intoice/water (200 mL) and the precipitated solid isolated by filtration, washed with water and sucked dry to give a pale yellow solid. This was recrystallised from 50:50 cyclohexane:ethyl acetate (30 mL) to give the title compound as an off—white solid (3.39 g, 55percent) . ‘H NMR(300 MHz, CDC13) : 3 10.39 (s, 1H) , 8.72 (d, 1H) , 8.29 (dd,1H) , 7.89 (d, 1H)
54.6%
at 0℃; for 4.66667 h;
Intermediate 17: l-(2-bromo-5-nitrophenyl)-N-methylmethanamine; Intermediate 17A:; [00237] Potassium nitrate (2.59 mL, 54.0 mmol) was added portionwise to a stirred and chilled (ice bath) solution of 2-bromobenzaldehyde (10 g, 54.0 mmol) in sulfuric acid (50 mL, 938 mmol) over 1 h. After 40 min an additional portion of KNO3 (0.72 g) was added. After 3 h stirring at 0 0C, the mixture was poured over ice water, and the product was filtered and washed with water. The crude pale yellow solid was recrystallized from 1 : 1 ethyl acetate/hexane (-60 mL) to give Intermediate 17A (6.789 g, 29.5 mmol, 54.6 percent yield). MS (ESI) m/z 230, 232 (M+H)+.
Reference:
[1] Patent: WO2014/186313, 2014, A1, . Location in patent: Page/Page column 173-174
[2] Patent: US2015/152108, 2015, A1, . Location in patent: Paragraph 0881; 0882
[3] Tetrahedron Letters, 2016, vol. 57, # 1, p. 11 - 14
[4] Organic and Biomolecular Chemistry, 2017, vol. 15, # 6, p. 1355 - 1362
[5] Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 20, p. 5051 - 5057
[6] Patent: WO2015/92431, 2015, A1, . Location in patent: Page/Page column 303
[7] Patent: WO2008/79836, 2008, A2, . Location in patent: Page/Page column 106
[8] European Journal of Organic Chemistry, 2011, # 28, p. 5626 - 5635
[9] Molecules, 2000, vol. 5, # 3, p. 227 - 239
[10] Patent: US5062884, 1991, A,
4
[ 373622-95-8 ]
[ 84459-32-5 ]
Reference:
[1] Journal of Medicinal Chemistry, 2016, vol. 59, # 15, p. 7125 - 7137
5
[ 943-14-6 ]
[ 84459-32-5 ]
Reference:
[1] Tetrahedron, 2006, vol. 62, # 18, p. 4563 - 4572
[2] Journal of the American Chemical Society, 2011, vol. 133, # 20, p. 7916 - 7925
[3] Journal of Medicinal Chemistry, 2016, vol. 59, # 15, p. 7125 - 7137
6
[ 33499-33-1 ]
[ 84459-32-5 ]
Reference:
[1] Journal of Organic Chemistry, 2011, vol. 76, # 15, p. 6414 - 6420
7
[ 99-61-6 ]
[ 84459-32-5 ]
Reference:
[1] Journal of Organic Chemistry, 2011, vol. 76, # 15, p. 6414 - 6420
8
[ 80887-01-0 ]
[ 84459-32-5 ]
Reference:
[1] Journal of Medicinal Chemistry, 2016, vol. 59, # 15, p. 7125 - 7137
With sodium tris(acetoxy)borohydride; acetic acid; In dichloromethane;
Step C 3-[(2-bromo-5-nitrophenyl)methyl]amino}propan-1-ol To a stirring solution of <strong>[84459-32-5]2-bromo-5-nitrobenzaldehyde</strong> (1 eq) in methylene chloride (0.1 M) at room temperature was added 3-amino-1-propanol (2 eq). After stirring for 4 hr, sodium triacetoxyborohydride (2 eq) and acetic acid (5 eq) was added. The reaction mixture was stirred for 3 hr and carefully quenched with methanol. The organic phase was washed with saturated sodium bicarbonate and brine. The organic phase was dried over anhydrous sodium sulfate, filtered, concentrated in vacuo and purified by flash chromatography (10% EtOAc/Hexane). EI-MS m/z 289 (M+H)+.
With potassium phosphate; copper(l) iodide; 1,10-Phenanthroline; In 1,4-dioxane; at 80℃;Schlenk technique;
General procedure: In an oven dried Schlenk tube, were added alcohol 1 (69.0-199.5 mg, 0.5 mmol), CuI (10 mol%)and 1,10-Phenanthroline (20 mol%) and K3PO4 (2 mmol) followed by the addition of dioxane (2mL) at room temperature under open air atmosphere. The stirred reaction mixture was heated inan oil bath at 80 C for 7-48 h. Progress of the reaction was monitored by TLC till the reaction iscompleted. Then, the reaction mixture was cooled to room temperature, quenched with aqueousNH4Cl solution and then extracted with CH2Cl2 (3 10 mL). The organic layer was washed withsaturated NaCl solution, dried (Na2SO4), and filtered. Evaporation of the solvent under reducedpressure and purification of the crude material by silica gel column chromatography (petroleumether/ethyl acetate) furnished the aldehyde/ketone 2 (61-97%).
With pyridinium chlorochromate; In dichloromethane;
Step B 2-Bromo-5-nitrobenzaldehyde To a stirring solution of (2-bromo-5-nitrophenyl) methan-1-ol (1 eq) in methylene chloride (0.1 M) at room temperature was added pyridinium chlorochromate (2 eq). After 2 hr the reaction mixture was filtered through celite and the product was purified by flash chromatography (15% EtOAc/Hexane). EI-MS m/z 230 (M+H)+.
b 2-Bromo-5-nitrocinnamic acid This reaction was carried out similarly to Example 1, with <strong>[84459-32-5]2-bromo-5-nitrobenzaldehyde</strong> and malonic acid in pyridine and with piperidine. The product of melting point 185 C. was obtained in 57% yield.
Intermediate 17; [00238] To a stirred solution of Intermediate 17A (17.768 g, 77 mmol) inMeOH (200 mL) was added methylamine (33 wt. % in EtOH) (21.81 mL, 232 mmol) dropwise and stirred for 1 h at 25 0C. Then, the reaction mixture was cooled to 0 0C and sodium borohydride (5.84 g, 154 mmol) was added portionwise with stirring. The reaction mixture was allowed to reach rt and stirred overnight. The reaction mixture was concentrated under reduced pressure, diluted with EtOAc (250 mL), washed with water (2x100 mL), brine (1x100 mL) and dried (Na2SO4). The solvent was removed under reduced pressure to give Intermediate 17 (18.134 g, 74.0 mmol, 96 % yield) as a yellow oil. Compound was pure (>95% by NMR) and utilized in the subsequent step without any further purification. MS (ESI) m/z 245.1 (M+H)+. 1H- <n="109"/>NMR: (500 MHz, CDCl3) delta ppm 2.51 (s, 3 H), 3.90 (s, 2 H), 7.73 (d, J=8.8 Hz, 1 H), 7.99 (dd, J=8.8, 2.7 Hz, 1 H), 8.32 (d, J=2.7 Hz, 1 H).
With N-Bromosuccinimide; 4-chloro-2-(trifluoromethyl)aniline; palladium diacetate; In 1,2-dichloro-ethane; trifluoroacetic acid; at 60℃; for 24h;
General procedure: Compound 1 (0.4 mol), N-bromosuccinimide (NBS) (0.48 mol, 85.4 mg), and Pd(OAc)2(10 mol%, 8.9 mg), 2-Amino-5-chlorobenzotrifluoride (20 mol%, 15.6 mg) were mixed withDCE (2.5 mL) and TFA (0.5 mL) solvent. The reaction mixture was stirred 24 h at 60 C. Aftercompletion of the reaction, the solution was concentrated in vacuo and purified by columnchromatography on silica gel using PE/DCM/EtOAc as eluent to give the desired product.
With sodium acetate; palladium diacetate; triphenylphosphine; In N,N-dimethyl-formamide; at 80℃; for 3h;
General procedure: 1a-1g (1mmol) and 2 (1.2 mmol) were heated at 80oC in presence of Pd(OAc)2 (10 mol%) , NaOAc (1.5 mmol) and PPh3 (0.25 mmol) in dry DMF (6 mL) for 3h. Then it was allowed to cool to r.t and extracted with EtOAc (3 x 20 mL).Then organic layer was washed with water and dried over Na2SO4 and concentrated in vacuum to get crude product which was then purified through column chromatography by using silica gel ( 60-120 mesh) and pet erther : EtOAc (20:1) as eluent
With palladium diacetate; caesium carbonate; triphenylphosphine; In N,N-dimethyl acetamide; at 90℃; for 3h;Inert atmosphere;
General procedure: o-Bromobenzaldehyde (50 mg, 0.273 mmol.), o-aminobenzeneboronicacid (53.5 mg, 1.2 equiv), Pd(OAc)2(5 mol%), Ph3P (0.25 equiv), and Cs2CO3 (133.5 mg, 1.5equiv) were added to a two-necked round-bottom flaskunder an argon atmosphere. Dry DMA (3 mL) was added tothe reaction mixture, and the solution was degassed withnitrogen and heated at 90 C for 3 h. Progress of the reactionwas monitored by TLC. On completion, the reaction mixturewas cooled to r.t. and diluted with H2O. It was then extractedwith EtOAc (3 × 50 mL), and the combined organic phaseswere washed with brine and dried over anhydrous Na2SO4.The solution was filtered and evaporated under reducedpressure, and the crude product was purified by columnchromatography on silica eluting with PE-EtOAc (5:1);yellow solid; mp 102-104 C (lit.9 104-106 C); yield 90%.
With ammonium hydroxide; copper(l) iodide; 1,10-Phenanthroline; triethylamine; In N,N-dimethyl-formamide; at 95℃; for 5h;Inert atmosphere;
General procedure: In a two necked round bottom flask a mixture of ortho-bromoaldehyde (100 mg, 0.54 mmol), phenylacetylene (66.10 mg, 0.648 mmol), aq. NH3 (2.5 M in DMF), Et3N (2 mmol), CuI (10 mol %), 9,10-Phenanthroline (0.25 mmol ) were taken in 3mL of DMF solvent in inert atmosphere. This mixture were heated to 95 oC temperature for 5 h. Completion of the reaction was confirmed by monitoring TLC. After the completion of the reaction themixture were cooled to room temperature and diluted with water and extracted with EtOAc (3×50 mL). Combined organic organic layer was washed with brine and dried over anhydrous Na2SO4. It was then evaporated under reduced pressure and desired product was isolated by column chromatography using silica gel mess and mixture of EtOAc and petroleum ether as eluents. Yellow Solid; mp: 105-107 oC;Yields : 88 %; 1H NMR (CDCl3, 200MHz): 7.47-7.60 (3H, s),7.68 (1H, t, J = 8.0 Hz), 8.20 (2H,dd, J1 = 1.2 Hz, J2 = 8.0 Hz), 8.31 (1H, d, J = 8.2 Hz), 8.60 (1H, dd, J1 = 0.8 Hz, J2 = 7.6 Hz), 8.96 (1H, s),9.50 (1H, s); 13C NMR (CDCl3, 50MHz): 111.9, 125.5,127.7(2C), 128.4, 129.1, 129.2 (2C), 129.5, 129.7,135.2, 138.9, 145.0, 153.2,155.2; Elemental Analysis: C: 71.99; H: 4.03; N: 11.19%; Found : C: 71.91; H: 3.98; N: 11.10%; HRMS of C15H11N2O2+[M+H+]: 251.0815; Observed : 251.0821.
With boron trifluoride diethyl etherate; niobium pentachloride; In dichloromethane; at -78 - 20℃;Inert atmosphere;
General procedure: NbCl5 (265 mg, 1.0 mmol) and boron trifluoride-diethyl etherate (0.83 mL, 1.20mmol) was dissolved in methylene dichloride (30 mL) at 78 C under nitrogen. Afteraddition of diarylphosphine (5.5 mmol) and aldehyde (5.0 mmol) to the mixture insequential order, the temperature was allowed to warm to rt, and the resulting mixturewas stirred overnight. Then mixture was washed with water and brine, and the organicphase was dried over MgSO4, filtered over celite and concentrated under vacuum. Theresidue was purified by silica gel chromatography with hexane/ethyl acetate to affordthe product as a white solid.