[dichloro(phenyl)methyl]benzene

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 25.6 mL of N,N-dimethylformamide (DMF) (manufactured by Wako Pure Chemical Industries Ltd.) was added to 60.1 g of benzophenone (manufactured by Wako Pure Chemical Industries Ltd., and then 60.2 mL of thionyl chloride (manufactured by Wako Pure Chemical Industries Ltd.) was added dropwise thereto, followed by performing a reaction at a reaction temperature of 75° C. for 12 hours. After confirming the production of the dichlorodiphenyl methane by means of 1H-NMR, 60 mL of toluene and 80 mL of water were added thereto under ice-cooling to perform liquid separation and remove the aqueous layer, thereby obtaining a dichlorodiphenyl methane/toluene solution. a reaction at a reaction temperature of 75° C. for 12 hours were added under ice-cooling liquid separation remove the aqueous layer

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-Bromo-6-methoxycatechol (3.87 g) and diphenyl-dichloromethane (4.61 g) were heated at 170° C. with stirring without a solvent. After being allowed to stand for cooling, a saturated aqueous solution of sodium bicarbonate was added to the mixture, followed by extraction with ether. The organic layer was washed with a saturated saline and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was triturated with methanol to give Compound IIbl-a (4.7 g, 69%) as a white solid. for cooling followed by extraction with ether The organic layer was washed with a saturated saline dried over anhydrous magnesium sulfate the solvent was distilled off under reduced pressure The residue was triturated with methanol to give Compound IIbl-a (4.7 g, 69%) as a white solid

Conditions: temp:170.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 3,4-dihydroxypropiophenone (ICN Biomedicals, Inc., 3300 Hyland Ave., Costa Mesa, Calif., 92626, USA, 5.0 g, 30 mmol) and dichlorodiphenylmethane (10.0 mL, 52.1 mmol) was heated for 7 min at 170° C. The reaction was cooled and poured into 1 N sodium hydroxide. The mixture was extracted with ether (2×) and the combined extracts were washed with water and brine. The organic layer was dried over magnesium sulfate and concentrated. The residue was flash chromatographed on silica gel (2×5 inches packed in hexane) with elution proceeding as follows: 2% ether/hexane (500 mL), 0.84 g of a white solid tentatively identified as 2-chloro-1-(2,2-diphenyl-benzo(1,3)dioxol-5-yl)-propan-1-one; 5% ether/hexane (250 mL), 1.9 g of an unidentified orange oil; 5% ether/hexane (250 mL), 2.18 g of recovered dichlorodiphenylmethane; 10% ether/hexane (500 mL), 4.82 g (48%) of 1-(2,2-diphenyl-benzo(1,3)dioxol-5-yl)-propan-1-one as an orange oil which solidified on standing. The product had: mp 69-70.5° C. Analysis calculated for C22H17ClO3 : C, 79.98; H, 5.49. Found: C, 80.05; H, 5.34. The reaction was cooled The mixture was extracted with ether (2×) the combined extracts were washed with water and brine The organic layer was dried over magnesium sulfate concentrated chromatographed on silica gel (2×5 inches packed in hexane) with elution proceeding

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-bromo-5-fluoro-benzene-1,2-diol (12 g, 58.0 mmol) and diphenyldichloromethane (1.2 eq., 16.50 g) was stirred at room temperature until gaseous evolution ceased. The mixture was heated with stirring at 180° C. for 20 min. The reaction mixture was allowed to cool to room temperature, diluted with methanol (50 ml) and vigorously stirred. The precipitated product was collected by filtration and dissolved in toluene (50 ml). Methanol (100 ml) was added and the mixture stirred 30 min at room temperature. The precipitated product was collected by filtration (yield 10.3 g, 48%), a further batch (6.4 g, 30%) was recovered from the mother liquors. The mixture was heated with stirring at 180° C. for 20 min to cool to room temperature vigorously stirred The precipitated product was collected by filtration dissolved in toluene (50 ml) Methanol (100 ml) was added the mixture stirred 30 min at room temperature The precipitated product was collected by filtration (yield 10.3 g, 48%) a further batch (6.4 g, 30%) was recovered from the mother liquors

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 25.6 mL of N,N-dimethylformamide (DMF) (manufactured by Wako Pure Chemical Industries Ltd.) was added to 60.1 g of benzophenone (manufactured by Wako Pure Chemical Industries Ltd., and then 60.2 mL of thionyl chloride (manufactured by Wako Pure Chemical Industries Ltd.) was added dropwise thereto, followed by performing a reaction at a reaction temperature of 75° C. for 12 hours. After confirming the production of the dichlorodiphenyl methane by means of 1H-NMR, 60 mL of toluene and 80 mL of water were added thereto under ice-cooling to perform liquid separation and remove the aqueous layer, thereby obtaining a dichlorodiphenyl methane/toluene solution. a reaction at a reaction temperature of 75° C. for 12 hours were added under ice-cooling liquid separation remove the aqueous layer

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution (1.25 M) of diethyl acetamidomalonate (13.33 g, 61.8 mmol) in N-methyl-2-pyrrolidone (40 mL) was added potassium t-butoxide (7.20 g, 64.3 mmol), and the mixture was stirred at room temperature for 1 hr. Diphenylmethylene chloride (10.0 g, 49.3 mmol) and potassium iodide (4.10 g, 24.7 mol) were added, and the mixture was stirred at 70° C. for 6 hrs. After completion of the reaction, 2M aqueous sodium hydroxide solution (45 mL) was added to the reaction mixture, and the mixture was stirred at 60° C. for 5 hrs. The reaction mixture was allowed to cool to room temperature and the mixture was partitioned. The aqueous layer was adjusted to pH 7.0 with concentrated hydrochloric acid (4.4 mL). Ethyl acetate (80 mL) was added, and then concentrated hydrochloric acid (6.9 mL) was added. The mixture was partitioned and the aqueous layer was extracted with ethyl acetate (40 mL). The organic layers were combined, successively washed with 2M hydrochloric acid (20 mL, three times) and saturated brine (10 mL), and concentrated. Toluene (30 mL) was added to the concentrated solution and the mixture was concentrated at 50° C. Toluene (30 mL) was added again, and the mixture was stirred for 30 min and cooled to 0° C. over 5 hrs, which resulted in the precipitation of white crystals. The crystals were collected by filtration and dried under reduced pressure to give the title compound (11.69 g). The powder X-ray (Cu—Kα ray) of the dry crystals showed characteristic peaks at 5.8°, 11.5°, 21.6°, 23.2° and 28.7°, as shown in FIG. 1. the mixture was stirred at 70° C. for 6 hrs was added to the reaction mixture the mixture was stirred at 60° C. for 5 hrs to cool to room temperature the mixture was partitioned Ethyl acetate (80 mL) was added concentrated hydrochloric acid (6.9 mL) was added The mixture was partitioned the aqueous layer was extracted with ethyl acetate (40 mL) successively washed with 2M hydrochloric acid (20 mL, three times) and saturated brine (10 mL) concentrated Toluene (30 mL) was added to the concentrated solution the mixture was concentrated at 50° C Toluene (30 mL) was added again the mixture was stirred for 30 min cooled to 0° C. over 5 hrs which resulted in the precipitation of white crystals The crystals were collected by filtration dried under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution (1.25 M) of diethyl acetamidomalonate (6.79 g, 31.25 mmol) in N-methyl-2-pyrrolidone (25 mL) was added 60% sodium hydride (1.25 g, 31.25 mmol), and the mixture was stirred at room temperature for 1 hr. Diphenylmethylene chloride (4.45 mL, 25.0 mmol) and potassium iodide (4.15 g, 25 mmol) were added, and the mixture was stirred at 50° C. for 7 hrs. After completion of the reaction, toluene (75 mL) and water (31.5 mL) were added to the reaction mixture, and the mixture was partitioned. The organic layer was washed twice with water (31.5 mL) and concentrated. Ethanol (31.5 mL) and 2M aqueous sodium hydroxide solution (37.5 mL) were added to the concentrated solution, and the mixture was stirred at 80° C. for 11 hrs and allowed to cool to 25° C. Toluene (9 mL) was added and the mixture was partitioned. The aqueous layer was concentrated to a half volume and adjusted to pH 1.1 with concentrated hydrochloric acid, which resulted in the precipitation of white crystals. The crystals were collected by filtration and dried under vacuum to give the title compound (5.0 g). the mixture was stirred at 50° C. for 7 hrs were added to the reaction mixture the mixture was partitioned The organic layer was washed twice with water (31.5 mL) concentrated Ethanol (31.5 mL) and 2M aqueous sodium hydroxide solution (37.5 mL) were added to the concentrated solution the mixture was stirred at 80° C. for 11 hrs to cool to 25° C Toluene (9 mL) was added the mixture was partitioned The aqueous layer was concentrated to a half volume resulted in the precipitation of white crystals The crystals were collected by filtration dried under vacuum

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution (1.25 M) of diethyl acetamidomalonate (13.33 g, 61.8 mmol) in N-methyl-2-pyrrolidone (40 mL) was added potassium t-butoxide (7.20 g, 64.3 mmol), and the mixture was stirred at room temperature for 1 hr. Diphenylmethylene chloride (10.0 g, 49.3 mmol) and potassium iodide (4.10 g, 24.7 mol) were added, and the mixture was stirred at 70° C. for 6 hrs. After completion of the reaction, 2M aqueous sodium hydroxide solution (45 mL) was added to the reaction mixture, and the mixture was stirred at 60° C. for 5 hrs. The reaction mixture was allowed to cool to room temperature and the mixture was partitioned. The aqueous layer was adjusted to pH 7.0 with concentrated hydrochloric acid (4.4 mL). Ethyl acetate (80 mL) was added, and then concentrated hydrochloric acid (6.9 mL) was added. The mixture was partitioned and the aqueous layer was extracted with ethyl acetate (40 mL). The organic layers were combined, successively washed with 2M hydrochloric acid (20 mL, three times) and saturated brine (10 mL), and concentrated. Toluene (30 mL) was added to the concentrated solution and the mixture was concentrated at 50° C. Toluene (30 mL) was added again, and the mixture was stirred for 30 min and cooled to 0° C. over 5 hrs, which resulted in the precipitation of white crystals. The crystals were collected by filtration and dried under reduced pressure to give the title compound (11.69 g). The powder X-ray (Cu—Kα ray) of the dry crystals showed characteristic peaks at 5.8°, 11.5°, 21.6°, 23.2° and 28.7°, as shown in FIG. 1. the mixture was stirred at 70° C. for 6 hrs was added to the reaction mixture the mixture was stirred at 60° C. for 5 hrs to cool to room temperature the mixture was partitioned Ethyl acetate (80 mL) was added concentrated hydrochloric acid (6.9 mL) was added The mixture was partitioned the aqueous layer was extracted with ethyl acetate (40 mL) successively washed with 2M hydrochloric acid (20 mL, three times) and saturated brine (10 mL) concentrated Toluene (30 mL) was added to the concentrated solution the mixture was concentrated at 50° C Toluene (30 mL) was added again the mixture was stirred for 30 min cooled to 0° C. over 5 hrs which resulted in the precipitation of white crystals The crystals were collected by filtration dried under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution (1.25 M) of diethyl acetamidomalonate (6.79 g, 31.25 mmol) in N-methyl-2-pyrrolidone (25 mL) was added 60% sodium hydride (1.25 g, 31.25 mmol), and the mixture was stirred at room temperature for 1 hr. Diphenylmethylene chloride (4.45 mL, 25.0 mmol) and potassium iodide (4.15 g, 25 mmol) were added, and the mixture was stirred at 50° C. for 7 hrs. After completion of the reaction, toluene (75 mL) and water (31.5 mL) were added to the reaction mixture, and the mixture was partitioned. The organic layer was washed twice with water (31.5 mL) and concentrated. Ethanol (31.5 mL) and 2M aqueous sodium hydroxide solution (37.5 mL) were added to the concentrated solution, and the mixture was stirred at 80° C. for 11 hrs and allowed to cool to 25° C. Toluene (9 mL) was added and the mixture was partitioned. The aqueous layer was concentrated to a half volume and adjusted to pH 1.1 with concentrated hydrochloric acid, which resulted in the precipitation of white crystals. The crystals were collected by filtration and dried under vacuum to give the title compound (5.0 g). the mixture was stirred at 50° C. for 7 hrs were added to the reaction mixture the mixture was partitioned The organic layer was washed twice with water (31.5 mL) concentrated Ethanol (31.5 mL) and 2M aqueous sodium hydroxide solution (37.5 mL) were added to the concentrated solution the mixture was stirred at 80° C. for 11 hrs to cool to 25° C Toluene (9 mL) was added the mixture was partitioned The aqueous layer was concentrated to a half volume resulted in the precipitation of white crystals The crystals were collected by filtration dried under vacuum

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution (1.25 M) of diethyl acetamidomalonate (13.33 g, 61.8 mmol) in N-methyl-2-pyrrolidone (40 mL) was added potassium t-butoxide (7.20 g, 64.3 mmol), and the mixture was stirred at room temperature for 1 hour. Diphenylmethylene chloride (10.0 g, 49.3 mmol) and potassium iodide (4.10 g, 24.7 mol) were added, and the mixture was stirred at 70° C. for 6 hours. After completion of the reaction, 2M aqueous sodium hydroxide solution (45 mL) was added to the reaction mixture, and the mixture was stirred for 5 hours at 60° C. After cooling to room temperature, the mixture was partitioned. The aqueous layer was adjusted to pH 7.0 with concentrated hydrochloric acid (4.4 mL), ethyl acetate (30 mL) and then concentrated hydrochloric acid (6.9 mL) were added, and the aqueous layer was extracted. The aqueous layer was further extracted with ethyl acetate (40 mL). The organic layers were combined, washed 3 times with 2M hydrochloric acid (20 mL), washed with saturated brine (10 mL), and concentrated. Toluene (30 mL) was added to the concentrate, and the mixture was concentrated at 50° C. Toluene (30 mL) was further added, and the mixture was stirred for 30 minutes. The mixture was cooled to 0° C. over 5 hours to allow precipitation of white crystals. The crystals were collected by filtration and dried under reduced pressure to give the title compound (11.69 g). The powder X-ray (Cu—Kα ray) of the dry crystals showed characteristic peaks at 5.8°, 11.5°, 21.6°, 23.2°, and 28.7°. the mixture was stirred at 70° C. for 6 hours was added to the reaction mixture the mixture was stirred for 5 hours at 60° C After cooling to room temperature the mixture was partitioned concentrated hydrochloric acid (6.9 mL) were added the aqueous layer was extracted The aqueous layer was further extracted with ethyl acetate (40 mL) washed 3 times with 2M hydrochloric acid (20 mL) washed with saturated brine (10 mL) concentrated Toluene (30 mL) was added to the concentrate the mixture was concentrated at 50° C Toluene (30 mL) was further added the mixture was stirred for 30 minutes The mixture was cooled to 0° C. over 5 hours precipitation of white crystals The crystals were collected by filtration dried under reduced pressure