6-chlorospiro[3H-chromene-2,1'-cyclobutane]-4-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: Triethyl phosphonoacetate (4.03 g, 17.897 mmol) was added over 15 min to a stirred and cooled mixture of sodium hydride (431 mg, 17.897 mmol) in anhydrous tetrahydrofuran (25 ml). The reaction mixture was stirred for 30 min and then added 6-Chlorospiro[chromene-2,1′-cyclobutan]-4(3H)-one (2 g, 8.948 mmol) in anhydrous tetrahydrofuran. The reaction mixture was stirred at the same temperature under nitrogen for 24 h. The reaction mixture was diluted with methanol and water and the product was extracted into ethyl acetate (3×100 ml). The organic layer was washed with water (100 ml), brine, dried (Na2SO4) and concentrated to give 3.54 g of the crude product which was used as such for the next step. cooled The reaction mixture was stirred for 30 min The reaction mixture was stirred at the same temperature under nitrogen for 24 h the product was extracted into ethyl acetate (3×100 ml) The organic layer was washed with water (100 ml), brine dried (Na2SO4) concentrated

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

実験手順: Triethyl phosphonoacetate (4.03 g, 17.897 mmol) was added over 15 min to a stirred and cooled mixture of sodium hydride (431 mg, 17.897 mmol) in anhydrous tetrahydrofuran (25 ml). The reaction mixture was stirred for 30 min and then added 6-Chlorospiro[chromene-2,1′-cyclobutan]-4(3H)-one (2 g, 8.948 mmol) in anhydrous tetrahydrofuran. The reaction mixture was stirred at the same temperature under nitrogen for 24 h. The reaction mixture was diluted with methanol and water and the product was extracted into ethyl acetate (3×100 ml). The organic layer was washed with water (100 ml), brine, dried (Na2SO4) and concentrated to give 3.54 g of the crude product which was used as such for the next step. cooled The reaction mixture was stirred for 30 min The reaction mixture was stirred at the same temperature under nitrogen for 24 h the product was extracted into ethyl acetate (3×100 ml) The organic layer was washed with water (100 ml), brine dried (Na2SO4) concentrated

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

実験手順: To a stirred solution of 5′-chloro-2′-hydroxy acetophenone (5.0 g, 29.308 mmol) in methanol (50 ml) was added pyrrolidine (4.16 g, 58.616 mmol) followed by cyclobutanone (4.1 g, 58.616 mmol) at room temperature. The reaction mixture was heated to reflux under nitrogen for 14 h. The solvent was evaporated under reduced pressure and the residue obtained was diluted with water (100 ml) and the mixture was acidified to pH 4.0. The mixture was extracted with chloroform (3×100 ml). The combined organic extracts were washed with water (100 ml), brine (50 ml) and dried over anhydrous sodium sulfate. The residue obtained after evaporation of the solvent was purified by silica gel column chromatography using 15% ethyl acetate in petroleum ether to give 6.3 g of the product as a white solid; 1H NMR (300 MHz, CDCl3) δ 1.69-1.88 (m, 5H), 1.96-2.04 (m, 1H), 2.88 (s, 2H), 6.91 (d, J=9.0 Hz, 1H), 7.38 (d, J=6.6 Hz, 1H), 7.76 (s, 1H). The reaction mixture was heated to reflux under nitrogen for 14 h The solvent was evaporated under reduced pressure the residue obtained The mixture was extracted with chloroform (3×100 ml) The combined organic extracts were washed with water (100 ml), brine (50 ml) dried over anhydrous sodium sulfate The residue obtained after evaporation of the solvent was purified by silica gel column chromatography

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Sodium borohydride (40 mmol) was added to a solution of 6-Chloro-3,4-dihydro-4-oxo-spiro[2H-1-benzopyran-2,1′-cyclobutane] (10 mmol) in methanol (10 ml). at about 0° C. and the reaction mixture was stirred at room temperature for about 2 h and compound was extracted in ethyl acetate. Organic layer was washed with water, brine and separated. It was then dried on anhydrous sodium sulfate and concentrated to afford the desired product as a white solid. compound was extracted in ethyl acetate Organic layer was washed with water, brine separated It was then dried on anhydrous sodium sulfate concentrated

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

実験手順: Triethyl phosphonoacetate (4.03 g, 17.897 mmol) was added over 15 min to a stirred and cooled mixture of sodium hydride (431 mg, 17.897 mmol) in anhydrous tetrahydrofuran (25 ml). The reaction mixture was stirred for 30 min and then added 6-Chlorospiro[chromene-2,1′-cyclobutan]-4(3H)-one (2 g, 8.948 mmol) in anhydrous tetrahydrofuran. The reaction mixture was stirred at the same temperature under nitrogen for 24 h. The reaction mixture was diluted with methanol and water and the product was extracted into ethyl acetate (3×100 ml). The organic layer was washed with water (100 ml), brine, dried (Na2SO4) and concentrated to give 3.54 g of the crude product which was used as such for the next step. cooled The reaction mixture was stirred for 30 min The reaction mixture was stirred at the same temperature under nitrogen for 24 h the product was extracted into ethyl acetate (3×100 ml) The organic layer was washed with water (100 ml), brine dried (Na2SO4) concentrated

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

実験手順: To a stirred solution of 5′-chloro-2′-hydroxy acetophenone (5.0 g, 29.308 mmol) in methanol (50 ml) was added pyrrolidine (4.16 g, 58.616 mmol) followed by cyclobutanone (4.1 g, 58.616 mmol) at room temperature. The reaction mixture was heated to reflux under nitrogen for 14 h. The solvent was evaporated under reduced pressure and the residue obtained was diluted with water (100 ml) and the mixture was acidified to pH 4.0. The mixture was extracted with chloroform (3×100 ml). The combined organic extracts were washed with water (100 ml), brine (50 ml) and dried over anhydrous sodium sulfate. The residue obtained after evaporation of the solvent was purified by silica gel column chromatography using 15% ethyl acetate in petroleum ether to give 6.3 g of the product as a white solid; 1H NMR (300 MHz, CDCl3) δ 1.69-1.88 (m, 5H), 1.96-2.04 (m, 1H), 2.88 (s, 2H), 6.91 (d, J=9.0 Hz, 1H), 7.38 (d, J=6.6 Hz, 1H), 7.76 (s, 1H). The reaction mixture was heated to reflux under nitrogen for 14 h The solvent was evaporated under reduced pressure the residue obtained The mixture was extracted with chloroform (3×100 ml) The combined organic extracts were washed with water (100 ml), brine (50 ml) dried over anhydrous sodium sulfate The residue obtained after evaporation of the solvent was purified by silica gel column chromatography