4-甲氧基苯乙醛

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Methyl 4-methoxyphenylacetate (5.58 g, 0.031 mol) was added to anhydrous toluene (75 mL) and the reaction mixture was kept at −70° C. Diisobutylaluminum hydride (1.0 M, 34 mL) in toluene was added over 25 min. The reaction mixture was stirred for another 20 min then a sodium-potassium-tartrate solution (100 mL) was added to the reaction mixture. The organic layer was separated and the water layer was extracted with ether. The combined organic layers were washed with water, brine, and dried over sodium sulfate. The crude compound was purified by column chromatography (hexane:EtOAc 4:1) to yield 4-methoxyphenylacetaldehyde (0.90 g, 19.3%). A mixture of 4-methoxyphenylacetaldehyde (0.40 g, 2.66 mmol), morpholine (0.232 g, 2.66 mmol), and benzotriazole (0.304 g, 2.56 mmol) in ether (20 mL) with 3 Å molecular sieves was stirred at rt overnight. The molecular sieves were removed by filtration and the solvent was removed. The crude product was used for next step reaction without further purification. Sodium hydride (0.125 g, 5.2 mmol, 60% in mineral oil) was added to the crude product with anhydrous THF (20 mL). The reaction mixture was stirred at reflux for 3 h. THF was removed and the residue was poured into cold water (60 mL) and extracted with hexane (2×80 mL). The organic layer was dried over sodium sulfate and the solvent was removed to give the enamine (0.60 g). 2-Chloropyridine-3-carbonylchloride (0.44 g, 2.5 mmol) in dry DCM (5 mL) was added to the enamine (0.60 g), followed by triethylamine (0.5 mL) in anhydrous DCM (15 mL) at −70° C. The reaction mixture was allowed to warm to rt overnight. The mixture was then poured into water, and the organic phase was washed with sodium bicarbonate and brine. The crude residue was purified by column chromatography (EtOAc:MeOH 5:1) to the desired intermediate (0.45 g). The intermediate (0.45 g, 1.25 mmol) was stirred in HCl (8.0 mL, 6 N) overnight at rt. The desired compound was filtered off and washed with large amounts of water. The crude product (0.24 g, 1.18 mmol) was mixed with pyridine hydrochloride (1.4 g) and heated to 180-190° C. for 3 h. The mixture was poured into water and stirred for 30 min. The solid was filtered off and further washed with water and hexane to give 140 mg of 3-(4-hydroxyphenyl)-4H-pyrano[2,3-b]pyridine-4-one (49.6%). MS (ES) m/z: 239.90; Mp. 262-264° C. was kept at −70° C The organic layer was separated the water layer was extracted with ether The combined organic layers were washed with water, brine dried over sodium sulfate The crude compound was purified by column chromatography (hexane:EtOAc 4:1)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 2.14 g of (5-cyano-3-benzofuranyl)methyltriphenylphosphonium chloride and 0.7 g of 4-methoxyphenylacetaldehyde were dissolved in a solvent mixture of 100 ml of tetrahydrofuran and 100 ml of ethanol. The thus prepared solution was mixed with 0.71 g of 1,8-diazabicyclo[5.4.0]-7-undecene and stirred for 24 hours. After distilling off the solvent, the resulting residue was purified by subjecting it to silica gel column chromatography using toluene as an elution solvent, thereby obtaining 0.86 g of yellow and oily 3-[3-(4-methoxyphenyl)-allyl]-5-benzofurancarbonitrile as a mixture of E and Z forms. The thus obtained E/Z mixture was dissolved in 100 ml of ethanol, and the solution was subjected to catalytic hydrogenation under normal pressure in the presence of 370 mg of 5% palladium carbon catalyst. Thereafter, the catalyst was removed by filtration, and the solvent was distilled off to obtain 0.6 g of 3-[3-(4-methoxyphenyl)-propyl]-5-benzofurancarbonitrile. The thus obtained methoxy compound was dissolved in 20 ml of dichloromethane. With stirring at -40° C., to the resulting solution was added dropwise 10 ml of a dichloromethane solution containing 0.4 ml of boron tribromide. The resulting mixture was warmed up to room temperature and stirred for 2 hours. The resulting reaction solution was poured into cold dilute hydrochloric acid and extracted with chloroform. After drying the resulting organic layer and distilling off the solvent, the thus obtained residue was purified by subjecting it to silica gel column chromatography using toluene as an elution solvent. In this way, 280 mg of 3-[3-(4-hydroxyphenyl)propyl]-5-benzofurancarbonitrile. After distilling off the solvent the resulting residue was purified

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of cyanoacetic acid (3.57 g), in water (20 ml) is added a solution of sodium hydroxide (2.08 g) in water (20 ml). The solution is diluted with glyme (70 ml), 4-methoxyphenyl acetaldehyde (3.0 g) is added and the mixture is left at room temperature for 6.0 hours. The glyme is evaporated in vacuo, and the residue is mixed with 10% hydrochloric acid (200 ml) and refluxed for 6.0 hours. After cooling, the mixture is extracted with ethyl acetate. The ethyl acetate extract is washed once with brine, dried, evaporated and the residue subjected to chromatography on a column of silica gel using chloroform-ethyl acetate mixtures for elution to afford 2.2 g of 3-[(4-methoxyphenyl)methyl]glutaric acid. Crystallization from a benzene-ethyl acetate-hexane mixture gives a specimen having a melting point 109°-110° C. is added The glyme is evaporated in vacuo the residue is mixed with 10% hydrochloric acid (200 ml) refluxed for 6.0 hours After cooling the mixture is extracted with ethyl acetate The ethyl acetate extract is washed once with brine dried evaporated for elution

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 4-methoxyphenyl ethanol (15.0 g, 98.2 mmol) in 150 mL of methylene chloride was stirred at 0° C. while Dess-Martin periodinane (50 g, 1.2 eq.) was added in small portions. The ice-bath was removed and the reaction was stirred at rt for 1 h. The reaction mixture was then diluted with methylene chloride (100 mL), washed with 10% sodium thiosulfate, saturated NaHCO3 solution, water, saturated NaCl solution, and dried over Na2SO4. The product was purified using silica gel chromatography (100% hexanes to 20% EtOAC/hexanes) to afford 5.3 g (34%) of 4-methoxyphenyl acetaldehyde. was added in small portions The ice-bath was removed The reaction mixture was then diluted with methylene chloride (100 mL) washed with 10% sodium thiosulfate, saturated NaHCO3 solution, water, saturated NaCl solution dried over Na2SO4 The product was purified