2-bromo-1-phenylhexan-1-one

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 α-bromohexanophenone (25.5 g, 0.1 mole), ammonium formate (22 g, 0.35 mole) and formic acid (110 mL) was refluxed with stirring for 3 h. The reaction mixture was poured onto ice and made basic with 10 N NaOH and extracted with ether. The organic layer was washed with water, dried over sodium sulfate and concentrated. The crude product was purified by flash chromatography on silica gel eluting with 20% ethyl acetate in hexane. To provide the desired compound as an oil (8.3 g, 41%); 1H NMR (δ, CDCl3, 400 MHz) 7.55 (m, 2H), 7.40 (s, 1H), 7.34 (dd, J=7,7 Hz, 2H), 7.22 (dd, J=7, 7 Hz, 1H), 2.74 (m, 2H), 1.6 (m, 2H), 1.30 (m, 2H), 0.84 (t, J=7 Hz, 3H) ppm. was refluxed The reaction mixture was poured onto ice extracted with ether The organic layer was washed with water dried over sodium sulfate concentrated The crude product was purified by flash chromatography on silica gel eluting with 20% ethyl acetate in hexane

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

実験手順: A mixture of α-bromohexanophenone (25.5 g, 0.1 mole), ammonium formate (22 g, 0.35 mole) and formic acid (110 mL) was refluxed with stirring for 3 h. The reaction mixture was poured onto ice and made basic with 10 N NaOH and extracted with ether. The organic layer was washed with water, dried over sodium sulfate and concentrated. The crude product was purified by flash chromatography on silica gel eluting with 20% ethyl acetate in hexane. To provide the desired compound as an oil (8.3 g, 41%); 1H NMR (δ, CDCl3, 400 MHz) 7.55 (m, 2H), 7.40 (s, 1H), 7.34 (dd, J=7,7 Hz, 2H), 7.22 (dd, J=7, 7 Hz, 1H), 2.74 (m, 2H), 1.6 (m, 2H), 1.30 (m, 2H), 0.84 (t, J=7 Hz, 3H) ppm. was refluxed The reaction mixture was poured onto ice extracted with ether The organic layer was washed with water dried over sodium sulfate concentrated The crude product was purified by flash chromatography on silica gel eluting with 20% ethyl acetate in hexane

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

実験手順: Anhydrous aluminium chloride (0.120 g.) is added to an ice-cooled solution of n-hexanophenone (21.1 g.) in anhydrous ether (20 ml.). The mixture is stirred and ice-cooled to a temperature below 10° C. during the dropwise addition of bromine (6.0 ml.) during 1 hour. The mixture is evaporated and the residual oil dissolved in ether (100 ml.). The solution obtained is washed first with a saturated aqueous solution of sodium thiosulphate (3 × 30 ml.) and then with water. After drying (sodium sulphate) the ethereal solution is evaporated to give α-bromo-n-hexanophenone as an oil (28.0 g.) which is used without further purification. The mixture is evaporated the residual oil dissolved in ether (100 ml.) The solution obtained is washed first with a saturated aqueous solution of sodium thiosulphate (3 × 30 ml.) After drying (sodium sulphate) the ethereal solution is evaporated

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

実験手順: Small portions of NaH (60%, 7.92 g, 198 mmol) are added to a solution of dimethyl malonate (22.6 ml, 198 mmol) in DMSO (100 mL) at 0° C. The ice bath is removed and the mixture stirred at room temperature for 2 hours. The solution is rechilled to 0° C. and a solution of 2-bromo-1-phenyl-hexan-1-one (2–1) (16.8 g, 66 mmol) in DMSO (50 mL) is added slowly. The ice bath is removed and the mixture stirred overnight. Water (500 mL) is added and the mixture is extracted with EtOAc (4×150 mL). The combined extracts are washed with brine (300 mL), dried (Na2SO4), and evaporated, to provide the product as a light yellow oil. LC-MS (M+1) 307. 1H NMR (δ, CDCl3) 7.98–8.02 (m, 2H), 7.46–7.60 (m, 3H), 4.18–4.28 (m, 1H), 4.03–4.12 (m, 1H), 3.80 (s, 3H), 3.6.1 (s, 3H), 1.55–1.63 (m, 2H), 1.02–1.20 (m, 4H), 0.76 (t, J=0.72 Hz, 3H). The ice bath is removed is rechilled to 0° C. The ice bath is removed the mixture stirred overnight Water (500 mL) is added the mixture is extracted with EtOAc (4×150 mL) The combined extracts are washed with brine (300 mL) dried (Na2SO4) evaporated

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

実験手順: A mixture of α-bromohexanophenone (25.5 g, 0.1 mole), ammonium formate (22 g, 0.35 mole) and formic acid (110 mL) is refluxed with stirring for 3 hours. The reaction mixture is poured onto ice, made basic with 10 N NaOH, and extracted with ether. The organic layer is washed with water, dried over sodium sulfate, and concentrated. The crude product is purified by flash chromatography on silica gel eluting with 20% ethyl acetate in hexane to provide the desired compound as an oil. 1H NMR (δ, CDCl3, 400 MHz) 7.55 (m, 2H), 7.40 (s, 1H), 7.34 (dd, J=7, 7 Hz, 2H), 7.22 (dd, J=7, 7 Hz, 1H), 2.74 (m, 2H), 1.6 (m, 2H), 1.30 (m, 2H), 0.84 (t, J=7 Hz, 3H) ppm. is refluxed The reaction mixture is poured onto ice extracted with ether The organic layer is washed with water dried over sodium sulfate concentrated The crude product is purified by flash chromatography on silica gel eluting with 20% ethyl acetate in hexane

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

実験手順: Anhydrous aluminum chloride (0.120 g.) is added to an ice-cooled solution of n-hexanophenone (21.1 g.) in anhydrous ether (20 ml.). The mixture is stirred and ice-cooled to a temperature below 10° C. during the dropwise addition of bromine (6.0 ml.) during 1 hour. The mixture is evaporated and the residual oil dissolved in ether (100 ml.). The solution obtained is washed first with a saturated aqueous solution of sodium thiosulphate (3× 30 ml.) and then with water. After drying (sodium sulphate) the ethereal solution is evaporated to give α-bromo-n-hexanophenone as an oil (28.0 g.) which is used without further purification. The mixture is evaporated the residual oil dissolved in ether (100 ml.) The solution obtained is washed first with a saturated aqueous solution of sodium thiosulphate (3× 30 ml.) After drying (sodium sulphate) the ethereal solution is evaporated

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

実験手順: A mixture of α-bromohexanophenone (25.5 g, 0.1 mole), ammonium formate (22 g, 0.35 mole) and formic acid (110 mL) was refluxed with stirring for 3 h. The reaction mixture was poured onto ice and made basic with 10 N NaOH and extracted with ether. The organic layer was washed with water, dried over sodium sulfate and concentrated. The crude product was purified by flash chromatography on silica gel eluting with 20% ethyl acetate in hexane. To provide the desired compound as an oil (8.3 g, 41 %); 1H NMR (δ, CDCl3, 400 MHz) 7.55 (m, 2H), 7.40 (s, 1H), 7.34 (dd, J=7,7 Hz, 2H), 7.22 (dd, J=7, 7 Hz, 1H), 2.74 (m, 2H), 1.6 (m, 2H), 1.30 (m, 2H), 0.84 (t, J=7 Hz, 3H) ppm. was refluxed The reaction mixture was poured onto ice extracted with ether The organic layer was washed with water dried over sodium sulfate concentrated The crude product was purified by flash chromatography on silica gel eluting with 20% ethyl acetate in hexane

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

実験手順: A mixture of α-bromohexanophenone (25.5 g, 0.1 mole), ammonium formate (22 g, 0.35 mole) and formic acid (110 mL) was refluxed with stirring for 3 h. The reaction mixture was poured onto ice and made basic with 10 N NaOH and extracted with ether. The organic layer was washed with water, dried over sodium sulfate and concentrated. The crude product was purified by flash chromatography on silica gel eluting with 20% ethyl acetate in hexane. To provide the desired compound as an oil (8.3 g, 41%); 1H NMR (δ, CDCl3, 400 MHz) 7.55 (m, 2H), 7.40 (s, 1H), 7.34 (dd, J=7,7 Hz, 2H), 7.22 (dd, J=7, 7 Hz, 1H), 2.74 (m, 2H), 1.6 (m, 2H), 1.30 (m, 2H), 0.84 (t, J=7 Hz, 3H) ppm. was refluxed The reaction mixture was poured onto ice extracted with ether The organic layer was washed with water dried over sodium sulfate concentrated The crude product was purified by flash chromatography on silica gel eluting with 20% ethyl acetate in hexane

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

実験手順: Small portions of NaH (60%, 7.92 g, 198 mmol) are added to a solution of dimethyl malonate (22.6 ml, 198 mmol) in DMSO (100 mL) at 0° C. The ice bath is removed and the mixture stirred at room temperature for 2 hours. The solution is rechilled to 0° C. and a solution of 2-bromo-1-phenyl-hexan-1-one (2-1) (16.8 g, 66 mmol) in DMSO (50 mL) is added slowly. The ice bath is removed and the mixture stirred overnight. Water (500 mL) is added and the mixture is extracted with EtOAc (4×150 mL). The combined extracts are washed with brine (300 mL), dried (Na2SO4), and evaporated, to provide the product as a light yellow oil. LC-MS (M+1) 307. 1H NMR (δ, CDCl3) 7.98-8.02 (m, 2H), 7.46-7.60 (m,3H), 4.18-4.28 (m, 1H), 4.03-4.12 (m, 1H), 3.80 (s, 3H), 3.6.1 (s, 3H), 1.55-1.63 (m, 2H), 1.02-1.20 (m, 4H), 0.76 (t, J=0.72 Hz, 3H). The ice bath is removed is rechilled to 0° C. The ice bath is removed the mixture stirred overnight Water (500 mL) is added the mixture is extracted with EtOAc (4×150 mL) The combined extracts are washed with brine (300 mL) dried (Na2SO4) evaporated

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

実験手順: A mixture of α-bromohexanophenone (25.5 g, 0.1 mole), ammonium formate (22 g, 0.35 mole) and formic acid (110 mL) is refluxed with stirring for 3 hours. The reaction mixture is poured onto ice, made basic with 10 N NaOH, and extracted with ether. The organic layer is washed with water, dried over sodium sulfate, and concentrated. The crude product is purified by flash chromatography on silica gel eluting with 20% ethyl acetate in hexane to provide the desired compound as an oil. 1H NMR (δ, CDCl3, 400 MHz) 7.55 (m, 2H), 7.40 (s, 1H), 7.34 (dd, J=7,7 Hz, 2H), 7.22 (dd, J=7, 7 Hz, 1H), 2.74 (m, 2H), 1.6 (m, 2H), 1.30 (m, 2H), 0.84 (t, J=7 Hz, 3H) ppm. is refluxed The reaction mixture is poured onto ice extracted with ether The organic layer is washed with water dried over sodium sulfate concentrated The crude product is purified by flash chromatography on silica gel eluting with 20% ethyl acetate in hexane

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

実験手順: A mixture of α-bromohexanophenone (25.5 g, 0.1 mole), ammonium formate (22 g, 0.35 mole) and formic acid (110 mL) was refluxed with stirring for 3 h. The reaction mixture was poured onto ice and made basic with 10 N NaOH and extracted with ether. The organic layer was washed with water, dried over sodium sulfate and concentrated. The crude product was purified by flash chromatography on silica gel eluting with 20% ethyl acetate in hexane. To provide the desired compound as an oil (8.3 g, 41%); 1H NMR (δ, CDCl3, 400 MHz) 7.55 (m, 2H), 7.40 (s, 1H), 7.34 (dd, J=7,7 Hz, 2H), 7.22 (dd, J=7, 7 Hz, 1H), 2.74 (m, 2H), 1.6 (m, 2H), 1.30 (m, 2H), 0.84 (t, J=7 Hz, 3H) ppm. was refluxed The reaction mixture was poured onto ice extracted with ether The organic layer was washed with water dried over sodium sulfate concentrated The crude product was purified by flash chromatography on silica gel eluting with 20% ethyl acetate in hexane