* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
4-(2-Bromoethyl)oxane To a stirring solution of 2-(4-oxanyl)ethyl methanesulfonate (11.9 g, 56.9 mmol) in dry acetone (300 mL) was added lithium bromide (29.7 g, 56.9 mmol). The reaction was refluxed under an N2 atmosphere for 5 h. The acetone was removed by rotary evaporation, water (150 mL) was added and the mixture was extracted with dichloromethane (2*100 mL). The combined extracts were dried (K2CO3), filtered and concentrated by rotary evaporation to yield a light brown oil. The crude compound was then distilled (65° C., 0.2 mm) to yield 8.06 g of a colorless oil (73.3percent yield).
46%
With lithium bromide In acetone at 50℃; for 5 h;
e) To a solution of 465 mg (2.2 mmol) of 2-(tetrahydro-2H-pyran-4-yl)ethyl methanesulfonate in 1 1 mL of acetone LiBr (970 mg, 1 1 .1 mmol) was added. The resulting mixture was stirred at 505C for 5 hours. Then, it was allowed to cool to room temperature and the solvent was evaporated. Water was added and the mixture was extracted with DCM (x3). The combined extracts were dried over MgS04, filtered and the solvent removed. The crude was purified by column chromatography over silica gel eluting with mixtures hexane/EtAcO. 4-(2- bromoethyl)tetrahydro-2H-pyran was obtained as a colorless oil (200 mg, 46percent).
With triethylamine; In dichloromethane; at 0 - 20℃;
d) To a solution of 300 mg (2.2 mmol) of <strong>[4677-18-3]2-(tetrahydro-2H-pyran-4-yl)ethanol</strong> in 10 mL of DCM at 05C TEA (0.38 mL, 2.7 mmol) and methanesulfonyl chloride (0.19 mL, 2.5 mmol) were added. The mixture was allowed to warm to room temperature and stirred at this temperature overnight. The reaction was stirred with saturated NaHC03 for 15 min and the aqueous phase was extracted with DCM (x3). The combined organic layers were dried over MgS04, filtered and concentrated to quantitatively yield 2-(tetrahydro-2H-pyran-4-yl)ethyl methanesulfonate as a colorless oil.
77.0%
With triethylamine; In dichloromethane;
2-(4-Oxanyl)ethyl methanesulfonate To a stirring solution of 2-(4-oxanyl)ethanol (9.63 g, 74.0 mmol) in dry dichloromethane (350 mL) was added distilled triethylamine (20.62 mL, 96.2 mmol) at 0 C., followed by drop-wise addition of methanesulfonyl chloride (7.44 mL, 96.2 mmol) over 15 min. The reaction was stirred for 16 h under N2 and slowly allowed to come to ambient temperature. The reaction was washed with saturated NaHCO3 (100 mL) and the aqueous phase was extracted with dichloromethane (1*50 mL). The combined organic extracts were dried (K2CO3), filtered and concentrated by rotary evaporation to yield 11.9 g of a colorless oil (77.0% yield).
With triethylamine; In dichloromethane; at 0 - 20℃; for 4h;
Mesyl chloride (2.9 g, 25.3 mmol) was added dropwise to a solution of 2- (tetrahydro-2H-pyran-4-yl)ethan-1-ol (2.9 g, 22.3 mmol) in dichloromethane (20 ml) and triethylamine (2.76 g, 27.3 mmol) at 0 C.Then reaction mixture was stirred at rt for 4 h. A saturated solution of sodium bicarbonate (10 ml) was added to the reaction mixture and the product was extracted with dichloromethane (3x20 ml). The combined organic layer was dried over anhydrous sodium sulphate and concentrated under reduced pressure to afford the title compound which was caffied forward to the next step without further purification.
With triethylamine; In dichloromethane; at 0 - 20℃;
Intermediate 33: 2-(Tetrahydro-2/-/-pyran-4-yl)ethyl methanesulfonate <n="72"/>To <strong>[4677-18-3]2-(tetrahydro-2H-pyran-4-yl)ethanol</strong> (3,3g) in dry dichloromethane (100 ml) at O0C and under nitrogen was added triethylamine (4.6 ml), followed by methanesulphonyl chloride (2.6 ml) dropwise over 5 minutes. The reaction was stirred until the ice in the bath melted and left overnight at room temperature. The reaction was washed with saturated aqueous sodium bicarbonate (40 ml). The organic layer was dried by passing through a hydrophobic frit and concentrated in vacuo to yield the title compound as a yellow oil (5.4g).1 H NMR (DMSO): 4.24 (2H, t), 3.82 (2H, m), 3.80 (3H, s), 3.27 (2H, m), 2.50 (5H, m), 1.60 (2H, m).
With triethylamine; In tetrahydrofuran; at 0 - 25℃; for 20h;
To a solution of 2-(tetrahydro-2H-pyran-4-yl)ethan-l-ol (300 mg, 2.304 mmol) and TEA (0.964 mL, 6.91 mmol) in THF (10 mL) was added dropwise Ms-Cl (0.269 mL, 3.46 mmol) at 0 C. The reaction mixture was stirred for 20 hours at 25 C. The reaction mixture was poured into water (20 mL), extracted by EtOAc (30 mL), washed with 1M HC1 (5 ml), sat NaHCCh, (10 ml) and brine (10 ml). The organic layer was dried over Na2S04, filtered and concentrated to give 2-(tetrahydro-2H-pyran-4-yl)ethyl methanesulfonate (300 mg, 1.329 mmol, 57.7 % yield) as a brown oil which was used in the next step without purification.
4-(2-Bromoethyl)oxane To a stirring solution of 2-(4-oxanyl)ethyl methanesulfonate (11.9 g, 56.9 mmol) in dry acetone (300 mL) was added lithium bromide (29.7 g, 56.9 mmol). The reaction was refluxed under an N2 atmosphere for 5 h. The acetone was removed by rotary evaporation, water (150 mL) was added and the mixture was extracted with dichloromethane (2*100 mL). The combined extracts were dried (K2CO3), filtered and concentrated by rotary evaporation to yield a light brown oil. The crude compound was then distilled (65 C., 0.2 mm) to yield 8.06 g of a colorless oil (73.3% yield).
46%
With lithium bromide; In acetone; at 50℃; for 5h;
e) To a solution of 465 mg (2.2 mmol) of 2-(tetrahydro-2H-pyran-4-yl)ethyl methanesulfonate in 1 1 mL of acetone LiBr (970 mg, 1 1 .1 mmol) was added. The resulting mixture was stirred at 505C for 5 hours. Then, it was allowed to cool to room temperature and the solvent was evaporated. Water was added and the mixture was extracted with DCM (x3). The combined extracts were dried over MgS04, filtered and the solvent removed. The crude was purified by column chromatography over silica gel eluting with mixtures hexane/EtAcO. 4-(2- bromoethyl)tetrahydro-2H-pyran was obtained as a colorless oil (200 mg, 46%).
With lithium bromide; In acetone; at 50℃;
To a solution of 2-(tetrahydro-2H-pyran-4-yl)ethyl methanesulfonate (4.5g, crude) in acetone (50 ml) was added lithium bromide (11.18 g, 129 mmol) and the resulting mixture was heated for 4 to 5 h at 50 C. The reaction solvent was evaporated under reduced pressure and the residue obtained was diluted with water and extracted with ethyl acetate. The combined organic layers were dried over anhydrous sodium sulphate and concentrated under reduced pressure to get crude product. Crude product was purified by column chromatography using mobile phase 0-65% ethyl acetate in hexane to afford the title compound. ?H NMR (400MHz, CDC13) & 4.0 1-3.97 (m, 2H), 3.49-3.39 (m, 4H), 1.86-1.76 (m, 3H), 1.65-1.62 (m, 2H), 1.37-1.36 (m, 2H).
With lithium bromide; In acetone; for 4h;Heating / reflux;
Intermediate 34: 4-(2-Bromoethyl)tetrahvdro-2H-pyranTo 2-(tetrahydro-2H-pyran-4-yl)ethyl methanesulfonate (5.4 g) in dry acetone at room temperature was added lithium bromide (9 g) in one go. The reaction was heated to reflux for 4 hours, under nitrogen. The reaction was cooled to room temperature and concentrated in vacuo. The residue was taken up in dichloromethane (100 ml) and washed with water (50 ml). The organic layer was dried by passing through a hydrophobic frit, and concentrated in vacuo. The product was purified by silica chromatography (40 g) (ISCO) using a gradient elution of 0-50 % cyclohexane:ethyl acetate to afford the title compound as a colourless oil (3.5g). 1 H NMR (DMSO): 3.82 (2H, m), 3.56 (2H, t), 3.26 (2H, m), 1.75 (2H, m), 1.65 (1 H, m), 1.57 (2H, m), 1.16 (2H, m).
5-chloro-6-(piperazin-1-yl)-2-[(2-tetrahydro-2H-pyran-4-ylethyl)sulfanyl]benzimidazole dihydrochloride[ No CAS ]
[ 144-55-8 ]
[ 428871-03-8 ]
Yield
Reaction Conditions
Operation in experiment
With hydrogenchloride In tetrahydrofuran; water; dimethyl sulfoxide
P.B Production method of 3-(tetrahydro-2H-pyran-4-yl)propanol
Production Example B Production method of 3-(tetrahydro-2H-pyran-4-yl)propanol To a solution of 185 mg of 2-(tetrahydro-2H-pyran-4-yl)ethyl methanesulfonate, which was used in Example 41, in dimethylsulfoxide (2 ml), 90 mg of sodium cyanide was added in nitrogen atmosphere, followed by 2 hours' stirring at 80ØC. Water was added to the reaction solution which then was extracted with ether. The ether layer was successively washed with water and saturated brine, dried on anhydrous sodium sulfate and the solvent was distilled off. To the residue 1 ml of conc. hydrochloric acid was added, followed by 12 hours' stirring at 100ØC. The solution was cooled to room temperature, and the solvent was distilled off under reduced pressure. To the residue 2 ml of 10% hydrogen chloride-in-methanol solution was added, followed by 2 hours' stirring at 80ØC. The solution was cooled to room temperature and the solvent was distilled off under reduced pressure. Saturated aqueous sodium hydrogencarbonate solution was added to the residue, which then was extracted with chloroform. The chloroform layer was dried on anhydrous sodium sulfate, and the solvent was distilled off. To a solution of so obtained residue in tetrahydrofuran (3 ml), 41 mg of lithium aluminum hydride was added at 0ØC in nitrogen atmosphere, followed by 30 minutes' stirring at the same temperature. To the solution 400 mg of sodium sulfate decahydrate was added and stirred for 1.5 hours at room temperature. The insoluble matter was filtered off, and the filtrate was concentrated under reduced pressure to provide 74 mg of the title compound.
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
110K+ Compounds
Competitive Price
1-2 Day Shipping
