2,2-二溴丙烷

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 1-(1-piperazinyl)-1-ethanone (6.7 g, 0.052 mol), dibromopropane (330 mL, excess) and K2CO3 (10.2 g, 0.079 mol) was stirred at rt for 4 h. The mixture was washed with 4×100 mL of water, and the organic phase (diluted with DCM) was acidified with aqueous hydrobromic acid (7 mL of 62% HBr dissolved in 150 mL of water). The organic layer was separated and washed with water (2×50 mL). The combined water layers were extracted with ether, neutralised (to pH 7) with 13 mL of 10 M NaOH, and then extracted with DCM. The combined organic layers were dried and concentrated in vacuo to give 4.1 g (32%) of the title compound. The mixture was washed with 4×100 mL of water the organic phase (diluted with DCM) The organic layer was separated washed with water (2×50 mL) The combined water layers were extracted with ether, neutralised (to pH 7) with 13 mL of 10 M NaOH extracted with DCM The combined organic layers were dried concentrated in vacuo

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 1-(1-piperazinyl)-1-ethanone (6.7 g, 0.052 mol), dibromopropane (330 mL, excess) and K2CO3 (10.2 g, 0.079 mol) was stirred at rt for 4 h. The mixture was washed with 4×100 mL of water, and the organic phase (diluted with DCM) was acidified with aqueous hydrobromic acid (7 mL of 62% HBr dissolved in 150 mL of water). The organic layer was separated and washed with water (2×50 mL). The combined water layers were extracted with ether, neutralised (to pH 7) with 13 mL of 10 M NaOH, and then extracted with DCM. The combined organic layers were dried and concentrated in vacuo to give 4.1 g (32%) of the title compound. The mixture was washed with 4×100 mL of water the organic phase (diluted with DCM) The organic layer was separated washed with water (2×50 mL) The combined water layers were extracted with ether, neutralised (to pH 7) with 13 mL of 10 M NaOH extracted with DCM The combined organic layers were dried concentrated in vacuo

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 98.4 g (0.45 mole) of 7-chlorodibenzofuran-3-ol, 200 ml of methyl ethyl ketone, 93 g (0.67 mole) of potassium carbonate and 283 g (1.4 moles) of dibromopropane was refluxed for 24 hours. The inorganic precipitate was filtered off with suction and the filtrate was concentrated under reduced pressure. The residue was dissolved in 500 ml of methylene chloride and the solution was washed with 100 ml of water, 100 ml of 2 N sodium hydroxide solution and 100 ml of water in succession, dried over sodium sulfate and concentrated under reduced pressure. The solid residue was left to stand with 30 ml of pentane at 0° C. for 30 minutes, filtered off with suction and washed with 30 ml of cold n-pentane. 77 g of pure 1-bromo-3-(7-chlorodibenzofuran-3-oxy)-propane of melting point 83°-85° C. were obtained; yield: 50% of theory. was refluxed for 24 hours The inorganic precipitate was filtered off with suction the filtrate was concentrated under reduced pressure The residue was dissolved in 500 ml of methylene chloride the solution was washed with 100 ml of water, 100 ml of 2 N sodium hydroxide solution and 100 ml of water in succession dried over sodium sulfate concentrated under reduced pressure The solid residue was left filtered off with suction washed with 30 ml of cold n-pentane

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 1-(1-piperazinyl)-1-ethanone (6.7 g, 0.052 mol), dibromopropane (330 mL, excess) and K2CO3 (10.2 g, 0.079 mol) was stirred at rt for 4 h. The mixture was washed with 4×100 mL of water, and the organic phase (diluted with DCM) was acidified with aqueous hydrobromic acid (7 mL of 62% HBr dissolved in 150 mL of water). The organic layer was separated and washed with water (2×50 mL). The combined water layers were extracted with ether, neutralised (to pH 7) with 13 mL of 10 M NaOH, and then extracted with DCM. The combined organic layers were dried and concentrated in vacuo to give 4.1 g (32%) of the title compound. The mixture was washed with 4×100 mL of water the organic phase (diluted with DCM) The organic layer was separated washed with water (2×50 mL) The combined water layers were extracted with ether, neutralised (to pH 7) with 13 mL of 10 M NaOH extracted with DCM The combined organic layers were dried concentrated in vacuo

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 1-(1-piperazinyl)-1-ethanone (6.7 g, 0.052 mol), dibromopropane (330 mL, excess) and K2CO3 (10.2 g, 0.079 mol) was stirred at rt for 4 h. The mixture was washed with 4×100 mL of water, and the organic phase (diluted with DCM) was acidified with aqueous hydrobromic acid (7 mL of 62% HBr dissolved in 150 mL of water). The organic layer was separated and washed with water (2×50 mL). The combined water layers were extracted with ether, neutralised (to pH 7) with 13 mL of 10 M NaOH, and then extracted with DCM. The combined organic layers were dried and concentrated in vacuo to give 4.1 g (32%) of the title compound. The mixture was washed with 4×100 mL of water the organic phase (diluted with DCM) The organic layer was separated washed with water (2×50 mL) The combined water layers were extracted with ether, neutralised (to pH 7) with 13 mL of 10 M NaOH extracted with DCM The combined organic layers were dried concentrated in vacuo

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 1-(1-piperazinyl)-1-ethanone (6.7 g, 0.052 mol), dibromopropane (330 mL, excess) and K2CO3 (10.2 g, 0.079 mol) was stirred at rt for 4 h. The mixture was washed with 4×100 mL of water, and the organic phase (diluted with DCM) was acidified with aqueous hydrobromic acid (7 mL of 62% HBr dissolved in 150 mL of water). The organic layer was separated and washed with water (2×50 mL). The combined water layers were extracted with ether, neutralised (to pH 7) with 13 mL of 10 M NaOH, and, then extracted with DCM. The combined organic layers were dried and concentrated in vacuo to give 4.1 g (32%) of the title compound. The mixture was washed with 4×100 mL of water the organic phase (diluted with DCM) The organic layer was separated washed with water (2×50 mL) The combined water layers were extracted with ether, neutralised (to pH 7) with 13 mL of 10 M NaOH extracted with DCM The combined organic layers were dried concentrated in vacuo

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 1-(1-piperazinyl)-1-ethanone (6.7 g, 0.052 mol), dibromopropane (330 mL, excess) and K2CO3 (10.2 g, 0.079 mol) was stirred at rt for 4 h. The mixture was washed with 4×100 mL of water, and the organic phase (diluted with DCM) was acidified with aqueous hydrobromic acid (7 mL of 62% HBr dissolved in 150 mL of water). The organic layer was separated and washed with water (2×50 mL). The combined water layers were extracted with ether, neutralised (to pH 7) with 13 mL of 10 M NaOH, and, then extracted with DCM. The combined organic layers were dried and concentrated in vacuo to give 4.1 g (32%) of the title compound. The mixture was washed with 4×100 mL of water the organic phase (diluted with DCM) The organic layer was separated washed with water (2×50 mL) The combined water layers were extracted with ether, neutralised (to pH 7) with 13 mL of 10 M NaOH extracted with DCM The combined organic layers were dried concentrated in vacuo

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution consisting of thienoic acid (10 g, 78 mmol) in THF (150 mL) at −78° C. was added an LDA solution (85 mL, 170 mmol, 2 M in heptanes/THF/ethylbenzene, Sigma-Aldrich) dropwise over 20 minutes, and the reaction mixture was stirred 40 minutes. To the reaction mixture was then added dibromopropane (23.8 g, 117 mmol) in one portion, and the reaction mixture was allowed to warm to room temperature and was stirred for 3 days. To the reaction mixture was added 50 mL each of a saturated aqueous solution of ammonium chloride, a saturated aqueous solution of sodium chloride, and 6 N HCl. The organic material was extracted with ethyl acetate and the organic layer was dried over sodium sulfate, filtered, and concentrated to afford the title compound as a yellow oil (24.0 g). The product was used without further purification; TLC Rf 0.5 (solvent system: 30:70:1 v/v ethyl acetate-hexanes-acetic acid). was stirred for 3 days The organic material was extracted with ethyl acetate the organic layer was dried over sodium sulfate filtered concentrated

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution consisting of thienoic acid (10 g, 78 mmol) in THF (150 mL) at −78° C. was added an LDA solution (85 mL, 170 mmol, 2 M in heptanes/THF/ethylbenzene, Sigma-Aldrich) dropwise over 20 minutes, and the reaction mixture was stirred 40 minutes. To the reaction mixture was then added dibromopropane (23.8 g, 117 mmol) in one portion, and the reaction mixture was allowed to warm to room temperature and was stirred for 3 days. To the reaction mixture was added 50 mL each of a saturated aqueous solution of ammonium chloride, a saturated aqueous solution of sodium chloride, and 6 N HCl. The organic material was extracted with ethyl acetate and the organic layer was dried over sodium sulfate, filtered, and concentrated to afford the title compound as a yellow oil (24.0 g). The product was used without further purification; TLC Rf 0.5 (solvent system: 30:70:1 v/v ethyl acetate-hexanes-acetic acid). was stirred for 3 days The organic material was extracted with ethyl acetate the organic layer was dried over sodium sulfate filtered concentrated

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 98.4 g (0.45 mole) of 7-chlorodibenzofuran-3-ol, 200 ml of methyl ethyl ketone, 93 g (0.67 mole) of potassium carbonate and 283 g (1.4 moles) of dibromopropane was refluxed for 24 hours, while stirring. The inorganic precipitate was filtered off under suction, the filtrate was evaporated down under reduced pressure, the residue was dissolved in 500 ml of methylene chloride, and the solution was washed with 100 ml of water, 100 ml of 2N sodium hydroxide solution and 100 ml of water in succession, dried over sodium sulfate and evaporated down under reduced pressure. The solid residue was left to stand with 30 ml of pentane at 0° C. for 30 minutes, after which it was filtered off under suction and washed with 30 ml of cold n-pentane. 77 g (50% of theory) of pure 1-bromo-3-(7-chlorodibenzofuran-3-yloxy)-propane of melting point 83°-85° C. were obtained. was refluxed for 24 hours The inorganic precipitate was filtered off under suction the filtrate was evaporated down under reduced pressure the residue was dissolved in 500 ml of methylene chloride the solution was washed with 100 ml of water, 100 ml of 2N sodium hydroxide solution and 100 ml of water in succession dried over sodium sulfate evaporated down under reduced pressure The solid residue was left after which it was filtered off under suction washed with 30 ml of cold n-pentane

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Methyl (2S)-2-[(1S)-5-hydroxy-2,3-dihydro-1H-inden-1-yl]propanoate (Example 14) (500 mg, 2.27 mmol), dibromopropane (4.308 g, 21.34 mmol), Cs2CO3 (834 mg, 2.56 mmol), and water (5 drops) were combined in DMF (20 mL) and stirred for 7 h at rt. The reaction mixture was concentrated under reduced pressure, water was added and the aqueous solution was extracted with EtOAc (2×). The combined organic phases were dried over Na2SO4, filtered, and concentrated under reduced pressure. Purification by silica gel flash chromatography (EtOAc/hexane (v/v)=1:25) gave 263 mg (34%) of the title compound as a colorless oil. 1H NMR (400 MHz, CDCl3): δ 1.08 (d, 3H), 1.91 (m, 1H), 2.17 (m, 1H), 2.32 (m, 2H), 2.80 (m, 1H), 2.88 (m, 2H), 3.51 (m, 1H), 3.61 (t, 2H), 3.72 (s, 3H), 4.08 (t, 2H), 6.69 (d, 1H), 6.76 (s, 1H), 6.98 (d, 1H). The reaction mixture was concentrated under reduced pressure, water was added the aqueous solution was extracted with EtOAc (2×) The combined organic phases were dried over Na2SO4 filtered concentrated under reduced pressure Purification by silica gel flash chromatography (EtOAc/hexane (v/v)=1:25)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Methyl (2S)-2-[(1S)-5-hydroxy-2,3-dihydro-1H-inden-1-yl]propanoate (Example 14) (500 mg, 2.27 mmol), dibromopropane (4.308 g, 21.34 mmol), Cs2CO3 (834 mg, 2.56 mmol), and water (5 drops) were combined in DMF (20 mL) and stirred for 7 h at rt. The reaction mixture was concentrated under reduced pressure, water was added and the aqueous solution was extracted with EtOAc (2×). The combined organic phases were dried over Na2SO4, filtered, and concentrated under reduced pressure. Purification by silica gel flash chromatography (EtOAc/hexane (v/v)=1:25) gave 263 mg (34%) of the title compound as a colorless oil. 1H NMR (400 MHz, CDCl3): δ 1.08 (d, 3H), 1.91 (m, 1H), 2.17 (m, 1H), 2.32 (m, 2H), 2.80 (m, 1H), 2.88 (m, 2H), 3.51 (m, 1H), 3.61 (t, 2H), 3.72 (s, 3H), 4.08 (t, 2H), 6.69 (d, 1H), 6.76 (s, 1H), 6.98 (d, 1H). The reaction mixture was concentrated under reduced pressure, water was added the aqueous solution was extracted with EtOAc (2×) The combined organic phases were dried over Na2SO4 filtered concentrated under reduced pressure Purification by silica gel flash chromatography (EtOAc/hexane (v/v)=1:25)