1-(5-chloro-2-hydroxyphenyl)ethanone

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A suspension of 5′-chloro-2′-hydroxyacetophenone (0.86 g, 5.0 mmol), potassium carbonate (1.4 g, 10 mmol) and 3-bromo-2-methylpropene (0.56 mL, 5.5 mmol) in anhydrous N,N-dimethylformamide (20 mL) was stirred at 60° C. for 4 hours. After cooling, the reaction mixture was diluted with water (100 mL), and the whole was extracted with ethyl acetate (100 mL). The organic layer was washed with saturated aqueous ammonium chloride solution (50 mL) and brine (50 mL) and dried over anhydrous magnesium sulfate. The solvent was removed in vacuo to give the title reference compound (1.1 g) as orange oil (Yield 96%). After cooling the whole was extracted with ethyl acetate (100 mL) The organic layer was washed with saturated aqueous ammonium chloride solution (50 mL) and brine (50 mL) dried over anhydrous magnesium sulfate The solvent was removed in vacuo

反応条件: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of lithium hexamethyldisilazide (800 mL of 1.0 M solution in THF, 800.0 mmol) was chilled to −78° C. under a nitrogen atmosphere. A solution of 5-chloro-2-hydroxyacetophenone (45.493 g, 266.67 mmol) in THF (130 mL) was added dropwise to the stirred solution over 0.5 hour. The reaction was held at −78° C. for 1 hour, warmed to −10° C. for 2 hours, warmed to 0° C. for 1 hour, then cooled to −78° C. Diethyl carbonate (35.54 mL, 34.65 g, 29.34 mmol) was added via syringe in one portion. The temperature was maintained at −78° C. for 0.5 hour, warmed to room temperature over 0.5 hour, and stirred for 3 hours. The crude reaction mixture was carefully poured over a mixture of rapidly stirred ice (1200 mL)/conc HCl (222 mL). The layers were separated and the aqueous phase was extracted with ethyl acetate. The combined organic phase was washed with brine, dried over Na2SO4, filtered and concentrated in vacuo yielding an oil that began to crystallize. Hexanes (150 mL) was added and crystallization proceeded. The crystalline product was collected by vacuum filtration to afford the title compound (29.04 g, 45%) as tan crystalline needles: mp 71.8-73.1° C. 1H NMR (CDCl3/300 MHz) 7.63 (d, 1H, J=2.4 Hz), 7.45 (dd, 1H, J=8.9, 2.6), 6.98 (d, 1H, J=8.9 Hz), 4.25 (q, 2H, J=7.3 Hz), 3.98 (s, 2H), 1.29 (t, 3H, 7.3 Hz). FABLRMS m/z 249 (M+Li). EIHRMS m/z 242.0346 (M+, Calc'd 242.0346). Anal. Calc'd for C11H11ClO4: C, 54.45; H, 4.57. Found: C, 54.48; H, 4.62. warmed to 0° C. for 1 hour cooled to −78° C The temperature was maintained at −78° C. for 0.5 hour warmed to room temperature over 0.5 hour The crude reaction mixture The layers were separated the aqueous phase was extracted with ethyl acetate The combined organic phase was washed with brine dried over Na2SO4 filtered concentrated in vacuo yielding an oil that to crystallize Hexanes (150 mL) was added crystallization The crystalline product was collected by vacuum filtration

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A 8.5 g quantity of 5'-chloro-2'-hydroxyacetophenone and 6.0 g of p-tolualdehyde were dissolved in 105 ml of ethanol. Then 17 ml of an aqueous solution containing 10 g of sodium hydroxide was slowly added thereto dropwise and stirred at room temperature for 4 hours. Then 350 ml of ethanol and 17 ml of an aqueous solution containing 3.5 g of sodium hydroxide were added to the reaction mixture, and 8.3 ml of a 30% aqueous hydrogen peroxide solution was further added dropwise slowly and stirred at room temperature for 12 hours. A 10% aqueous HCl solution was added to adjust the reaction mixture to pH 3. The crystals precipitated were collected by filtration and washed serially with 10 ml of water, 5 ml of ethanol and 10 ml of diethyl ether, thus giving 6.0 g of 6-chloro-3-hydroxy-2-(4-methylphenyl)-4H-1-benzopyran-4-one as crystals. was slowly added was further added dropwise slowly stirred at room temperature for 12 hours The crystals precipitated were collected by filtration washed serially with 10 ml of water, 5 ml of ethanol and 10 ml of diethyl ether

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A 8.5 g quantity of 5'-chloro-2'-hydroxyacetophenone and 6.0 g of p-tolualdehyde were dissolved in 105 ml of ethanol. Then 17 ml of an aqueous solution containing 10 g of sodium hydroxide was slowly added thereto dropwise and stirred at room temperature for 4 hours. Then 350 ml of ethanol and 17 ml of an aqueous solution containing 3.5 g of sodium hydroxide were added to the reaction mixture, and 8.3 ml of a 30% aqueous hydrogen peroxide solution was further added dropwise slowly and stirred at room temperature for 12 hours. A 10% aqueous HCl solution was added to adjust the reaction mixture to pH 3. The crystals precipitated were collected by filtration and washed serially with 10 ml of water, 5 ml of ethanol and 10 ml of diethyl ether, thus giving 6.0 g of 6-chloro-3-hydroxy-2-(4-methylphenyl)-4H-1-benzopyran-4-one as crystals. was slowly added was further added dropwise slowly stirred at room temperature for 12 hours The crystals precipitated were collected by filtration washed serially with 10 ml of water, 5 ml of ethanol and 10 ml of diethyl ether

反応条件: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Dissolve 5′-chloro-2′-hydroxyacetophenone (15.3594 g, 90.03 mmol) in 100 mL of anhydrous acetonitrile in a pressure vessel. Add K2CO3 (13.7541 g, 99.52 mmol) and MeI (25.56 mL, 180.06 mmol) to the vessel. Seal the vessel and heat the reaction mixture to 85° C. for 18 hours. Cool the reaction and concentrate it in vacuo. Partition the residue between Et2O and H2O. Wash the organic layers with 2N NaOH (2×). Dry the combined organic layers with MgSO4. Filter off the drying agent and concentrate in vacuo to afford 13.15 g of 1-(5-chloro-2-methoxy-phenyl)-ethanone (79%). Seal the vessel Cool the reaction concentrate it in vacuo Partition the residue between Et2O and H2O Wash the organic layers with 2N NaOH (2×) Dry the combined organic layers with MgSO4 Filter off the drying agent concentrate in vacuo

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Add 2-iodopropane (63.3 mL, 633 mmol) dropwise to a suspension of 1-(5-chloro-2-hydroxyphenyl)ethanone (90.0 g, 528 mmol) and potassium carbonate (109.46 g, 792 mmol) in DMF (1000 mL) at room temperature under nitrogen and heat the mixture at 80° C. for 22 hours. Cool and filter the mixture and remove the solvent reduced pressure. Dilute the residue with ethyl acetate (1 L), wash with water (300 mL) and brine (200 mL), dry over sodium sulfate, and remove the solvent under reduced pressure to afford 1-(5-chloro-2-isopropoxyphenyl)ethanone (104.78 g, 93%). Cool filter the mixture remove the solvent reduced pressure Dilute the residue with ethyl acetate (1 L) wash with water (300 mL) and brine (200 mL) dry over sodium sulfate remove the solvent under reduced pressure

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Add 2-iodopropane (63.3 mL, 633 mmol) dropwise to a suspension of 1-(5-chloro-2-hydroxyphenyl)ethanone (90.0 g, 528 mmol) and potassium carbonate (109.46 g, 792 mmol) in DMF (1000 mL) at room temperature under nitrogen and heat the mixture at 80° C. for 22 hours. Cool and filter the mixture and remove the solvent reduced pressure. Dilute the residue with ethyl acetate (1 L), wash with water (300 mL) and brine (200 mL), dry over sodium sulfate, and remove the solvent under reduced pressure to afford 1-(5-chloro-2-isopropoxyphenyl)ethanone (104.78 g, 93%). Cool filter the mixture remove the solvent reduced pressure Dilute the residue with ethyl acetate (1 L) wash with water (300 mL) and brine (200 mL) dry over sodium sulfate remove the solvent under reduced pressure

反応条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 3-(piperidin-1-ylsulfonyl)benzohydrazide (65 mg, 0.229 mmol) and 1-(5-chloro-2-hydroxyphenyl)ethanone (39.1 mg, 0.229 mmol) was dissolved in methanol (Volume: 4 ml) in the presence of acetic acid as a catalyst and then the reaction mixture was heated via microwave irradiation to 120° C. for 30 min. Reaction was monitored by TLC. After completion of the reaction, following cooling, the solvent was removed by vacuum and the resulting crude material was purified by flash column chromatography (2% CH3OH/CH2Cl2) afforded the product (E)-N′-(1-(5-chloro-2-hydroxyphenyl)ethylidene)-3-(piperidin-1-ylsulfonyl)benzohydrazide (55 mg, 0.124 mmol, 53.9% yield) as a solid. 1H NMR (CDCl3, 400 MHz): δ 8.09 (m, 2H), 7.85 (d, 1H, J=8.0 Hz), 7.62 (t, 1H, J=8.0 Hz), 7.41 (d, 1H, J=2.4 Hz), 7.22 (d, 1H, J=8.0 Hz), 6.93 (d, 1H, J=8.8 Hz), 2.97 (m, 4H), 2.41 (s, 3H), 1.61 (m, 4H), 1.40 (m, 2H). Mass [M+H]+:436.9 Reaction After completion of the reaction following cooling the solvent was removed by vacuum the resulting crude material was purified by flash column chromatography (2% CH3OH/CH2Cl2)