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HCL (25 mL, 6 mol/L) was added to compound 21 (1.0 g, 3.7 mmol), and stirred at 90 °C for 4 h. After cooling in air, the resultant solid was filtered, washed with water and dried to give compound 22 (0.80 g, 3.5 mmol, 95percent yield).Comment1H NMR (300 MHz, DMSO-d6) δ 10.01 (s, 1H), 7.34 (s, 1H), 7.11 (s, 1H), 3.83 (s, 3H).
50 g
With hydrogenchloride In water at 90℃; for 10 h;
A mixture of 140 (66 g, 243 mmoi) in 6 N 1-ICI aqueous solution (1.0 L) is stirred at 9() °C for 10 hours and then cooled to room temperature. The solid is collected by filtration, washed with water, and dried to give Ci as a white solid (50 g, 90percent yield). (MS:[MH-HJ 232.2)
Reference:
[1] Bioorganic and Medicinal Chemistry, 2011, vol. 19, # 22, p. 6892 - 6905
[2] Helvetica Chimica Acta, 1989, vol. 72, # 7, p. 1554 - 1582
[3] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1993, # 17, p. 1967 - 1972
[4] Journal of the American Chemical Society, 2014, vol. 136, # 6, p. 2583 - 2591
[5] Journal of Structural Chemistry, 2015, vol. 56, # 2, p. 346 - 351[6] Zh. Strukt. Kim., 2015, vol. 56, # 2, p. 361 - 366,6
[7] Patent: WO2017/176812, 2017, A1, . Location in patent: Paragraph 0401
HCL (25 mL, 6 mol/L) was added to compound 21 (1.0 g, 3.7 mmol), and stirred at 90 C for 4 h. After cooling in air, the resultant solid was filtered, washed with water and dried to give compound 22 (0.80 g, 3.5 mmol, 95% yield).Comment1H NMR (300 MHz, DMSO-d6) delta 10.01 (s, 1H), 7.34 (s, 1H), 7.11 (s, 1H), 3.83 (s, 3H).
With hydrogenchloride; water; at 90℃; for 4h;
Vanillin was suspended in methylene chloride, and then acetic anhydride and pyridine were added. The resultant solution was stirred at room temperature for 18 h. Water was added to the reaction mixture, and ethyl acetate was then added. The organic layer was washed with 1 N HCl, a saturated sodium hydrogen carbonate aqueous solution, and saturated brine, and was dried with anhydrous sodium sulfate. The organic layer was filtered, and concentrated under reduced pressure to give the pure compound a. The compound a and potassium bromide were suspended in water, and then bromine was added at 0 C. The solution was stirred at room temperature for 15 h. The resultant solid was filtered, washed with water, and dried to give the pure compound b. HCL was added to the compound b, and stirred at 90 C for 4 h. After cooling in the air, the resultant solid was filtered, washed with water, and dried to give the compound c. The equivocal compound c and substituted aromatic amine in methanol or acetonitrile was stirred for 4-6 h at room temperature, and then the reaction mixture was concentrated under reduced pressure, recrystallized from ethanol to give vanillin derivatives 1-3.
50 g
With hydrogenchloride; In water; at 90℃; for 10h;
A mixture of 140 (66 g, 243 mmoi) in 6 N 1-ICI aqueous solution (1.0 L) is stirred at 9() C for 10 hours and then cooled to room temperature. The solid is collected by filtration, washed with water, and dried to give Ci as a white solid (50 g, 90% yield). (MS:[MH-HJ 232.2)
With potassium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In DMF (N,N-dimethyl-formamide); water; at 80℃;
To a mixture of 4-acetoxy-2-bromo-5-methoxybenzaldehyde(273 mg, 1 mmol), 194 mg (1 mmol) of 2-ethoxycarbonylphenyl boronic acid and 276 mg (2 mmol) of K2CO3 in 5 mL of DMF and 1 mL of H2O was added 73.1 mg (0.1 mmol) of Pd(dppf)Cl2. The mixture was heated at 80 C. overnight. After the removal of the catalyst via filtration, the mixture was repartitioned between EtOAc and H2O. Aqueous layer was extracted 3 times with EtOAc and organic layers were combined and dried over Na2SO4. After the removal of the solvent, the residue was chromatographed to give 217 mg of 2?-Formyl-5?-hydroxy-4?-methoxy-biphenyl-2-carboxylic acid ethyl ester(3 with ortho substitution, scheme 6; 72%).Mass Spectrum: 301 (M+1).
A solution of aldehyde 9 (2.34 g, 8.6 mmol), boronic acid 11 (2.64 g, 10.3 mmol), tri-o-tolylphosphine (0.303 g, 1 mmol), and sodium bicarbonate (2.93 g, 34.9 mmol) in a mixture of dimethoxyethane (50 mL) and water (16 mL) was degassed by bubbling nitrogen through the solution for 15 min. Palladium (II) acetate (0.194 g, 0.864 mmol) was added and the reaction mixture was heated at 90 C for 2 h. The reaction mixture was cooled to room temperature. Methanol (20 mL), water (20 mL), and potassium carbonate (1.2 g, 17 mmol) were added, and the reaction mixture was stirred at room temperature for 1 h. The reaction mixture was filtered (Whatman Autovial 0.45 uM glass microfiber filter) and concentrated on a rotary evaporator. Ethyl acetate was added and the remaining aqueous layer was acidified with conc. HCl to pH 2-3. The aqueous layer was extracted three times with ethyl acetate. The combined organics were washed with water and brine, dried, and concentrated. The residue was chromatographed (silica gel, 30 to 50% ethyl acetate in hexanes) to afford compound 12 as a white solid (2.79 g, 7.7 mmol, 89%). 1H NMR (300 MHz, CDCl3) delta 9.77 (s, 1H), 8.15 (d, J = 8.4 Hz, 2H), 7.56 (s, 1H), 7.49-7.36 (m, 7H), 6.96 (s, 1H), 5.40 (s, 2H), 4.02 (s, 3H). ESI-MS m/z 363 [M+H]+