7-chloro-3,4-dihydro-2H-naphthalen-1-one

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:24.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of 7-chloro-1-tetralone CAS: 26673-32-5 (5.0 g; 27.68 mmol) in methanol (55 ml) was added pyridine (2.87 ml; 34.05 mmol) followed by a portion wise addition of methoxyamine hydrochloride (2.84 g; 34.05 mmol). The reaction mixture was stirred at 24° C. for 16 h under nitrogen. Methanol was removed under reduced pressure, the residue poured in water (300 ml) and 1N hydrochloric acid was added (100 ml). The solution was extracted with dichloromethane (3×150 ml). Combined organic layers were washed with water (300 ml) and dried over sodium sulfate. The solvent was removed in vacuo to afford 6.22 g (100% of theory) of crude 7-chloro-3,4-dihydro-2H-naphthalen-1-one-O-methyl-oxime as a brown oil. Methanol was removed under reduced pressure the residue poured in water (300 ml) 1N hydrochloric acid was added (100 ml) The solution was extracted with dichloromethane (3×150 ml) Combined organic layers were washed with water (300 ml) dried over sodium sulfate The solvent was removed in vacuo

反応条件: temp:24.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of 7-chloro-1-tetralone CAS: 26673-32-5 (5.0 g; 27.68 mmol) in methanol (55 ml) was added pyridine (2.87 ml; 34.05 mmol) followed by a portion wise addition of methoxyamine hydrochloride (2.84 g; 34.05 mmol). The reaction mixture was stirred at 24° C. for 16 h under nitrogen. Methanol was removed under reduced pressure, the residue poured in water (300 ml) and 1N hydrochloric acid was added (100 ml). The solution was extracted with dichloromethane (3×150 ml). Combined organic layers were washed with water (300 ml) and dried over sodium sulfate. The solvent was removed in vacuo to afford 6.22 g (100% of theory) of crude 7-chloro-3,4-dihydro-2H-naphthalen-1-one-O-methyl-oxime as a brown oil. Methanol was removed under reduced pressure the residue poured in water (300 ml) 1N hydrochloric acid was added (100 ml) The solution was extracted with dichloromethane (3×150 ml) Combined organic layers were washed with water (300 ml) dried over sodium sulfate The solvent was removed in vacuo

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

実験手順: 7-Amino-1-tetralone (500 mg, 3.1 mmol) was suspended in 3 mL of water and treated with 3 mL of concentrated hydrochloric acid with stirring. The mixture was cooled in an ice bath and treated dropwise with vigorous stirring with a solution of 241 mg of sodium nitrite in 1.5 mL of water (3.5 mmol, 1.1eq). The mixture was stirred at 0°-5° for 15 minutes then added dropwise to a cold solution of 366 mg of CuCl (3.7 mmol, 1.2 eq) in 6 mL of concentrated hydrochloric acid. The mixture was stirred for 5 minutes at 0° and 1 hour at room temperature. The mixture was extracted with methylene chloride (3×15 mL); the combined extracts were washed with brine, dried over magnesium sulfate, filtered and evaporated to dryness under vacuum at room temperature to give 550 mg (3.05 mmol, 98%) of the product, 1H NMR (300MHz, CDCl3): 2.16 (m,2H), 2.67 (t,6Hz,2H), 2.95 (t,6Hz,2H), 7.22 (d,8Hz,1H), 7.44 (dd;2,8Hz;1H), 8.01 (d,2Hz,1H). FAB-MS: calculated for C10H9C10 180; found 181 (M+H,10%). The mixture was cooled in an ice bath treated dropwise The mixture was stirred at 0°-5° for 15 minutes The mixture was stirred for 5 minutes at 0° and 1 hour at room temperature The mixture was extracted with methylene chloride (3×15 mL) the combined extracts were washed with brine dried over magnesium sulfate filtered evaporated to dryness under vacuum at room temperature

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

実験手順: 4-(4-Chlorophenyl)butyric acid (26.62 g) was added to 150 g of hot polyphosphoric acid (90° C.); the mixture was maintained at 90°-95° C. for 0.33 hour. After cooling to room temperature, the reaction mixture was added to 400 mL of ice-cold stirred water. The solution was allowed to warm to room temperature; and the resulting precipitate was filtered, washed (water) and air dried to give a pale yellow solid (22.3 g). The solid was recrystallized from toluene (50 mL) at -10° C. The crystals were collected and washed with cold toluene and then hexanes to give the tetralone as pale yellow crystals (18.18 g); mp 100.3°-101.1° C. the mixture was maintained at 90°-95° C. for 0.33 hour to warm to room temperature and the resulting precipitate was filtered washed (water) and air dried

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

実験手順: 4-(4-Chlorophenyl)butyric acid (26.62 g) was added to 150 g of hot polyphosphoric acid (90° C.); the mixture was maintained at 90°-95° C. for 0.33 hour. After cooling to room temperature, the reaction mixture was added to 400 mL of ice-cold stirred water. The solution was allowed to warm to room temperature; and the resulting precipitate was filtered, washed (water) and air dried to give a pale yellow solid (22.3 g). The solid was recrystallized from toluene (50 mL) at -10° C. The crystals were collected and washed with cold toluene and then hexanes to give the tetralone as pale yellow crystals (18.18 g); mp 100.3°-101.1° C. the mixture was maintained at 90°-95° C. for 0.33 hour to warm to room temperature and the resulting precipitate was filtered washed (water) and air dried

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

実験手順: Using general procedure A (Exp. 1.1), 7-chloro-3,4-dihydro-2H-naphthalen-1-one (Lit. 13) was reacted with MeMgI to give 6-chloro-4-methyl-1,2-dihydro-naphthalene as a yellow oil. MS: 178.0 ([M]+).

反応条件: temp:24.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of 7-chloro-1-tetralone CAS: 26673-32-5 (5.0 g; 27.68 mmol) in methanol (55 ml) was added pyridine (2.87 ml; 34.05 mmol) followed by a portion wise addition of methoxyamine hydrochloride (2.84 g; 34.05 mmol). The reaction mixture was stirred at 24° C. for 16 h under nitrogen. Methanol was removed under reduced pressure, the residue poured in water (300 ml) and 1N hydrochloric acid was added (100 ml). The solution was extracted with dichloromethane (3×150 ml). Combined organic layers were washed with water (300 ml) and dried over sodium sulfate. The solvent was removed in vacuo to afford 6.22 g (100% of theory) of crude 7-chloro-3,4-dihydro-2H-naphthalen-1-one-O-methyl-oxime as a brown oil. Methanol was removed under reduced pressure the residue poured in water (300 ml) 1N hydrochloric acid was added (100 ml) The solution was extracted with dichloromethane (3×150 ml) Combined organic layers were washed with water (300 ml) dried over sodium sulfate The solvent was removed in vacuo

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: 7-Chloro-α-tetralone (15.0 g), 8.75 g of dimethylamine hydrochloride, 3.25 g of paraformaldehyde, and 17.5 ml of 95% ethanol containing 0.2 ml of concentrated hydrogen chloride are combined and heated on a steam bath for 2 hours. The warm solution is transferred to a wide-mouthed flask, diluted with 200 ml of acetone, and allowed to stand at room temperature for several hours. The resultant crystals are collected and crystallized from acetone/ethanol to give 10.7 g of the title compound, melting point 169°-170° C. heated on a steam bath for 2 hours The warm solution is transferred to a wide-mouthed flask to stand at room temperature for several hours The resultant crystals are collected crystallized from acetone/ethanol

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

実験手順: Titanium isopropoxide (710 mg, 0.74 mls, 2.5 mmol) is added to a mixture of 7-chloro-1-tetralone (360 mg, 2 mmol) and 2-aminothiazoline (224 mg, 2.2 mmol). The reaction mixture is stirred for 16 hours at room temperature, then diluted with dry methanol (5 ml). Excess sodium borohydride is added carefully portionwise over a period of 45 minutes. The reaction mixture is stirred for a further 2 hours, then added to a saturated aqueous solution of Rochelle's salt and extracted with dichloromethane (2×25 mls). The organic phases are combined, washed sequentially with water and saturated brine, then filtered through a pad of magnesium sulphate. The filtrate is concentrated under reduced pressure to give the crude product as a pale yellow gum. The crude product is purified by column chromatography on silica, eluting with ethyl acetate to give the title compound as a white solid Mp 164-6° C. Nmr data: (CDCl3): 7.39 (1H, s, CH), 7.13 (1H, dd, CH), 7.01 (1H, s, CH), 4.90 (1H, m, CH), 4.06 (2H, m), 3.37 (2H, m), 2.72 (2H, m), 2.08 (1H, m), 1.85 (3H, m) The reaction mixture is stirred for a further 2 hours extracted with dichloromethane (2×25 mls) washed sequentially with water and saturated brine filtered through a pad of magnesium sulphate The filtrate is concentrated under reduced pressure to give the crude product as a pale yellow gum The crude product is purified by column chromatography on silica eluting with ethyl acetate

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

実験手順: 7-Amino-1-tetralone (500 mg, 3.1 mmol) was suspended in 3 mL of water and treated with 3 mL of concentrated hydrochloric acid with stirring. The mixture was cooled in an ice bath and treated dropwise with vigorous stirring with a solution of 241 mg of sodium nitrite in 1.5 mL of water (3.5 mmol, 1.1 eq). The mixture was stirred at 0°-5° for 15 minutes then added dropwise to a cold solution of 366 mg of CuCl (3.7 mmol, 1.2 eq) in 6 mL of concentrated hydrochloric acid. The mixture was stirred for 5 minutes at 0° and 1 hour at room temperature. The mixture was extracted with methylene chloride (3×15 mL); the combined extracts were washed with brine, dried over magnesium sulfate, filtered and evaporated to dryness under vacuum at room temperature to give 550 mg (3.05 mmol, 98%) of the product. 1H NMR (300 MHz, CDCl3): 2.16 (m,2H), 2.67 (t,6 Hz,2H), 2.95 (t,6 Hz,2H), 7.22 (d,8 Hz,1H), 7.44 (dd;2,8 Hz;1H), 8.01 (d,2 Hz,1H). FAB-MS: calculated for C10H9ClO 180; found 181 (M+H,10%). The mixture was cooled in an ice bath treated dropwise The mixture was stirred at 0°-5° for 15 minutes The mixture was stirred for 5 minutes at 0° and 1 hour at room temperature The mixture was extracted with methylene chloride (3×15 mL) the combined extracts were washed with brine dried over magnesium sulfate filtered evaporated to dryness under vacuum at room temperature