1-(4-chlorophenyl)-2-phenylethanone

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:; See reaction.notes.procedure_details.

実験手順: A mixture of 1-(4-chlorophenyl)-2-phenylethanone (350 mg, 1.52 mmol), 3-ethoxy-4-hydroxy-5-nitrobenzaldehyde (320 mg, 1.52 mmol), and urea (272 mg, 4.53 mmol) in anhydrous EtOH (15 mL) was added concentrated HCl solution (0.5 mL), and the reaction mixture was refluxed for overnight. TLC (EtOAc:MeOH=10:1) showed that about 30% of starting materials were consumed, and the reaction mixture was concentrated. The residue was purified by column chromatography (EtOAc:MeOH=40:1) and preparative HPLC to afford the product Compound 36 as a yellow solid (55.1 mg, yield: 7.8%). 1H NMR (DMSO-d6 400 MHz): δ 10.30 (s, 1H), 8.79 (s, 1H), 7.55 (s, 1H), 7.42 (s, 1H), 7.30 (d, J=8.4 Hz, 2H), 7.20 (d, J=8.4 Hz, 2H), 7.18 (s, 1H), 7.00-7.10 (m, 3H), 6.82 (d, J=7.2 Hz, 2H), 5.20 (d, J=2.4 Hz, 1H), 4.00-4.10 (m, 2H), 1.33 (t, J=6.8 Hz, 3H); MS (ESI): m/z 466.0 [M+1]+. the reaction mixture was refluxed for overnight were consumed the reaction mixture was concentrated The residue was purified by column chromatography (EtOAc:MeOH=40:1) and preparative HPLC

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: In a 1000 ml round bottomed flask equipped with a reflux condensor was placed 100 g 4-chlorophenyl benzyl ketone (0.43 mole), 400 ml of methanol, 50 ml of 37% formalin (0.67 mole), 5 g of piperidine, and 5 g of acetic acid. The resulting mixture was refluxed for 2 hours, concentrated in vacuo, partitioned between ethyl ether and water, washed with water, dried over anhydrous magnesium sulfate and concentrated in vacuo to yield 98 g of 2-phenyl 4'-chlorophenyl acrylophenone, an oil. In a 1000 ml round bottomed flask equipped with a reflux condensor The resulting mixture was refluxed for 2 hours concentrated in vacuo partitioned between ethyl ether and water washed with water dried over anhydrous magnesium sulfate concentrated in vacuo

反応条件: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a 2 liter 4 necked flask equipped with a mechanical stirrer thermometer, and reflux condensor was added 155 g (1.0 mole) of phenyl acetyl chloride and 500 ml (4.9 mole) of chlorobenzene. A total of 145 g (1.08 mole) of anhydrous aluminum chloride was added portionwise over 10 minutes. The mixture self warmed to 55° C. and evolved HCl gas over the course of the next 30 minutes. The mixture was stirred at about 50° C. for an additional 30 minutes and then poured onto about 500 g of ice and 110 ml of concentrated aqueous HCl. The organic layer (lower) was separated and the aqueous layer was washed with ethyl ether. The combined organic layers were washed with water, dilute aqueous NaOH, and water and then concentrated in vacuo. The resulting crude solid was recrystallized from 2200 ml of hexane yielding 132 g of 4-chlorophenyl benzyl ketone, mp 85°-90° C. reflux condensor over the course of the next 30 minutes The organic layer (lower) was separated the aqueous layer was washed with ethyl ether The combined organic layers were washed with water, dilute aqueous NaOH, and water concentrated in vacuo The resulting crude solid was recrystallized from 2200 ml of hexane yielding 132 g of 4-chlorophenyl benzyl ketone, mp 85°-90° C.

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

実験手順: A mixture of 1-(4-chlorophenyl)-2-phenylethanone (350 mg, 1.52 mmol), 3-ethoxy-4-hydroxy-5-nitrobenzaldehyde (320 mg, 1.52 mmol), and urea (272 mg, 4.53 mmol) in anhydrous EtOH (15 mL) was added concentrated HCl solution (0.5 mL), and the reaction mixture was refluxed for overnight. TLC (EtOAc:MeOH=10:1) showed that about 30% of starting materials were consumed, and the reaction mixture was concentrated. The residue was purified by column chromatography (EtOAc:MeOH=40:1) and preparative HPLC to afford the product Compound 36 as a yellow solid (55.1 mg, yield: 7.8%). 1H NMR (DMSO-d6 400 MHz): δ 10.30 (s, 1H), 8.79 (s, 1H), 7.55 (s, 1H), 7.42 (s, 1H), 7.30 (d, J=8.4 Hz, 2H), 7.20 (d, J=8.4 Hz, 2H), 7.18 (s, 1H), 7.00-7.10 (m, 3H), 6.82 (d, J=7.2 Hz, 2H), 5.20 (d, J=2.4 Hz, 1H), 4.00-4.10 (m, 2H), 1.33 (t, J=6.8 Hz, 3H); MS (ESI): m/z 466.0 [M+1]+. the reaction mixture was refluxed for overnight were consumed the reaction mixture was concentrated The residue was purified by column chromatography (EtOAc:MeOH=40:1) and preparative HPLC

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

実験手順: A solution of benzyl 4-chlorophenyl ketone (10.0 g, 43.3 mmol) and dimethylformamide dimethylacetal (23 mL, 173 mmol) in DMF (125 mL) was heated at 75° C. for 20 h. The volatiles were removed in vacuo to provide 3-dimethylamino-1-(4-chlorophenyl)-2-(phenyl)prop-2-en-1-one (43.3 mmol assumed) which was used directly in the next step. 1HNMR (CDCl3): δ 2.76 (s, 6H), 7.15 (m, 2H), 7.16-7.3 (m, 5H), 7.36 (m, 2H), 7.41 (s, 1H). The volatiles were removed in vacuo

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

実験手順: A solution of benzyl 4-chlorophenyl ketone (10.0 g, 43.3 mmol) and dimethylformamide dimethylacetal (23 mL, 173 mmol) in DMF (125 mL) was heated at 75° C. for 20 h. The volatiles were removed in vacuo to provide 3-dimethylamino-1-(4-chlorophenyl)-2-(phenyl)prop-2-en-1-one (43.3 mmol assumed) which was used directly in the next step. 1HNMR (CDCl3): δ 2.76 (s, 6H), 7.15 (m, 2H), 7.16-7.3 (m, 5H), 7.36 (m, 2H), 7.41 (s, 1H). The volatiles were removed in vacuo

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

実験手順: Under a nitrogen atmosphere, 2.45 g (25.7 mmol) of anhydrous magnesium chloride and 20 mL of dry THF were put into a 100-mL Schlenk flask and then stirred. To this mixed solution, 10.6 mL (21.2 mmol) of a solution of sodium cyclopentadienide having a concentration of 2.0 mol/L in THF was added. Then, the product was heated and refluxed for an hour, the obtained pink slurry was cooled in an ice bath, and a solution in which 3.5 g (17.8 mmol) of benzyl(p-chlorophenyl)ketone had been dissolved in 15 mL of dry THF was subsequently added thereto. Then, the product was stirred at room temperature for 18 hours, and the obtained orange solution was quenched with dilute aqueous hydrochloric acid. Then, 30 mL of diethyl ether was added thereto, the soluble part in diethyl ether was extracted, and the organic phase was neutralized and washed with an aqueous solution of saturated sodium hydrogen carbonate, water, and a saturated salt solution and then dehydrated with anhydrous magnesium sulfate. The solvent was distilled off, the residue was subsequently purified by silica gel column chromatography to obtain an objective that was a reddish orange solid (amount: 2.7 g), and the objective was directly used in the subsequent process. Then, the product was heated refluxed for an hour the obtained pink slurry was cooled in an ice bath was subsequently added Then, the product was stirred at room temperature for 18 hours the obtained orange solution was quenched with dilute aqueous hydrochloric acid Then, 30 mL of diethyl ether was added the soluble part in diethyl ether was extracted washed with an aqueous solution of saturated sodium hydrogen carbonate, water The solvent was distilled off the residue was subsequently purified by silica gel column chromatography to obtain an objective that

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

実験手順: A benzene solution containing 51.2 g 4-chlorophenylacetic acid and 39.3 g thionyl chloride is refluxed for 6 hours and the solvent removed. The crude reaction product is added dropwise to a slurry of 40 g aluminum chloride in 200 ml benzene maintaining the temperature below 50° C. After addition the reaction is refluxed for 1.5 hours. After cooling, the mixture is poured into ice and the resulting white solid is separated yielding 61.3 g of crude product. The product is taken up in methylene chloride and washed with 5% sodium hydroxide solution followed by water, dried over sodium sulfate and stripped yielding 49.3 g (71%) of >95% pure 4'-chlorodeoxybenzoin. 15 g of 4-chlorodeoxybenzoin is dissolved in 105 ml pyridine. An aqueous solution containing 15 g potassium permanganate is added and the reaction stirred for 6 hours at room temperature using dry ice to buffer the pH near 7. The mixture is extracted with methylene chloride, the extract washed with water, dried over Na2SO4 and stripped. The residue is recrystallized from ethanol yielding 6.1 g of white plate-like crystals which is identified as starting material. Concentration of the mother liquor yields 4 g of 4-chlorobenzil. is added The mixture is extracted with methylene chloride the extract washed with water dried over Na2SO4 The residue is recrystallized from ethanol yielding 6.1 g of white plate-like crystals which

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

実験手順: A mixture of 1-(4-chlorophenyl)-2-phenylethanone (350 mg, 1.52 mmol), 3-ethoxy-4-hydroxy-5-nitrobenzaldehyde (320 mg, 1.52 mmol), and urea (272 mg, 4.53 mmol) in anhydrous EtOH (15 mL) was added concentrated HCl solution (0.5 mL), and the reaction mixture was refluxed for overnight. TLC (EtOAc:MeOH=10:1) showed that about 30% of starting materials were consumed, and the reaction mixture was concentrated. The residue was purified by column chromatography (EtOAc:MeOH=40:1) and preparative HPLC to afford the product Compound 36 as a yellow solid (55.1 mg, yield: 7.8%). 1H NMR (DMSO-d6 400 MHz): δ 10.30 (s, 1H), 8.79 (s, 1H), 7.55 (s, 1H), 7.42 (s, 1H), 7.30 (d, J=8.4 Hz, 2H), 7.20 (d, J=8.4 Hz, 2H), 7.18 (s, 1H), 7.00-7.10 (m, 3H), 6.82 (d, J=7.2 Hz, 2H), 5.20 (d, J=2.4 Hz, 1H), 4.00-4.10 (m, 2H), 1.33 (t, J=6.8 Hz, 3H); MS (ESI): m/z 466.0 [M+1]+. the reaction mixture was refluxed for overnight were consumed the reaction mixture was concentrated The residue was purified by column chromatography (EtOAc:MeOH=40:1) and preparative HPLC