4-bromobutyl acetate

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:

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:

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

実験手順: Compound 3 was prepared by following a previously reported method. {Santra, 2004 #6} Briefly, diethyl malonate 1 (10 g, 62.5 mmol). 4-bromobutyl acetate 2 (15.84 g, 81.3 mmol) were placed in a round bottom flask containing acetonitrile (120 mL) and stirred for 2 min at room temperature. Then to this, we added potassium carbonate (34.5 g, 250.1 mmol) and refluxed for 36 h. Next, the mixture was filtered and the filtrate was concentrated to obtain a yellow liquid. This was extracted with ethyl acetate, and washed with water. The organic layers were combined and dried over Na2SO4, and purified by column chromatography using 4% ethyl acetate in petroleum ether as the eluent. refluxed for 36 h Next, the mixture was filtered the filtrate was concentrated to obtain a yellow liquid This was extracted with ethyl acetate washed with water dried over Na2SO4 purified by column chromatography

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

実験手順: A mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (9.5 g, 41 mmol), K2CO3 (7.2 g, 51 mmol), and 4-bromobutyl acetate (10 g, 51 mmol) in acetonitrile (200 ml) was heated at reflux for 3.5 hours. At the end of the reaction, the solution was cooled and filtered. The inorganic salt was washed with DCM (50 ml). The organic solvent was removed. The residue was purified on a flash chromatography column (packed with Sorbsil C30 silica gel, 100 g, eluted with DCM, 1 liter, increasing methanol from 2 to 4%, 2.51). The material thus purified weighted 12.92 g (89%). A small sample (1.67 g) was dissolved in ethanol and treated with 1 equivalent of fumaric acid (580 mg) in ethanol to yield white crystals: 1.8 g, m.p.=142-143° C. was heated at reflux for 3.5 hours At the end of the reaction the solution was cooled filtered The inorganic salt was washed with DCM (50 ml) The organic solvent was removed The residue was purified on a flash chromatography column (packed with Sorbsil C30 silica gel, 100 g, eluted with DCM, 1 liter, increasing methanol from 2 to 4%, 2.51) A small sample (1.67 g) was dissolved in ethanol to yield white crystals

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

実験手順: A mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (9.5 g, 41 mmol), K2CO3 (7.2 g, 51 mmol), and 4-bromobutyl acetate (10 g, 51 mmol) in acetonitrile (200 ml) was heated at reflux for 3.5 hours. At the end of the reaction, the solution was cooled and filtered. The inorganic salt was washed with DCM (50 ml). The organic solvent was removed. The residue was purified on a flash chromatography column (packed with Sorbsil C30 silica gel, 100 g, eluted with DCM, 1 liter, increasing methanol from to 4%, 2.51). The material thus purified weighed 12.92 g (89%). A small sample (1.67 g) was dissolved in ethanol and treated with 1 equivalent of fumaric acid (580 mg) in ethanol to yield white crystals: 1.8 g, m.p.=142°-143° C. was heated at reflux for 3.5 hours At the end of the reaction the solution was cooled filtered The inorganic salt was washed with DCM (50 ml) The organic solvent was removed The residue was purified on a flash chromatography column (packed with Sorbsil C30 silica gel, 100 g, eluted with DCM, 1 liter, increasing methanol from to 4%, 2.51) The material thus purified A small sample (1.67 g) was dissolved in ethanol to yield white crystals

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

実験手順: A mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (9.5 g, 41 mmol), K2CO3 (7.2 g, 51 mmol), and 4-bromobutyl acetate (10 g, 51 mmol) in acetonitrile (200 ml) was heated at reflux for 3.5 hours. At the end of the reaction, the solution was cooled and filtered. The inorganic salt was washed with DCM (50 ml). The organic solvent was removed. The residue was purified on a flash chromatography column (packed with Sorbsil C30 silica gel, 100 g, eluted with DCM, 1 liter, increasing methanol from 2 to 4%, 2.51). The material thus purified weighed 12.92 g (89%). A small sample (1.67 g) was dissolved in ethanol and treated with 1 equivalent of fumaric acid (580 mg) in ethanol to yield white crystals: 1.8 g, m.p.=142°-143° C. was heated at reflux for 3.5 hours At the end of the reaction the solution was cooled filtered The inorganic salt was washed with DCM (50 ml) The organic solvent was removed The residue was purified on a flash chromatography column (packed with Sorbsil C30 silica gel, 100 g, eluted with DCM, 1 liter, increasing methanol from 2 to 4%, 2.51) The material thus purified A small sample (1.67 g) was dissolved in ethanol to yield white crystals

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In 10 mL of anhydrous dimethylformamide was dissolved 920 mg (2 mmol) of 4-(4-hydroxy-4-(2-hydroxyphenyl)piperidino)-N,N-dimethyl-2,2-diphenylbutaneamide. To the resulting solution were added 585 g (3 mmol) of 4-bromobutylacetate, 414 mg (3 mmol) of potassium carbonate and a small amount of potassium iodide. The resulting mixture was stirred under heating at 80° C. for 4 hours. After cooling, the reaction mixture was poured into water, followed by extraction with ethyl acetate, washing with water and drying. The residue obtained by distilling off the solvent under reduced pressure was dissolved in 15 mL of methanol. To the resulting solution was added 3 mL of a 1N aqueous solution of sodium hydroxide, followed by stirring at room temperature for 1 hour. From the reaction mixture, the solvent was distilled off under reduced pressure. The residue thus obtained was dissolved in chloroform. The resulting solution was washed with water and dried. The residue obtained by distilling off the solvent under reduced pressure was purified by chromatography on a silica gel column, whereby 260 mg (yield: 24.5%) of 4-(4-hydroxy-4-(2-(4-hydroxybutyloxy)phenyl)piperidino)-N,N-dimethyl-2,2-diphenylbutaneamide (Compound No. 34) was obtained. After cooling followed by extraction with ethyl acetate washing with water drying The residue obtained by distilling off the solvent under reduced pressure was dissolved in 15 mL of methanol To the resulting solution was added 3 mL of a 1N aqueous solution of sodium hydroxide by stirring at room temperature for 1 hour From the reaction mixture, the solvent was distilled off under reduced pressure The residue thus obtained The resulting solution was washed with water dried The residue obtained by distilling off the solvent under reduced pressure was purified by chromatography on a silica gel column