1,3-dibromopropan-2-ol

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

実験手順: 1,3-dibromo-2-propanol (2.18 g.) is added to a stirred suspension of the salt obtained by mixing 2.7 g. benzyl mercaptan and sodium hydride (56% dispersion in mineral oil; 900 mg.) in 50 ml. dry tetrahydrofuran. After 2 hours at room temperature, the solvent is removed and 20 ml. of water is added to the residue. The resultant aqueous mixture is extracted with ether and the extracts washed with water, dried over magnesium sulfate and evaporated to yield 1,3-bis(benzylthio)-2-propanol. obtained by mixing 2.7 g the solvent is removed of water is added to the residue The resultant aqueous mixture is extracted with ether the extracts washed with water dried over magnesium sulfate evaporated

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

実験手順: 1,3-dibromo-2-propanol (2.18 g.) is added to a stirred suspension of the salt obtained by mixing 2.7 g. benzyl mercaptan and sodium hydride (56% dispersion in mineral oil; 900 mg.) in 50 ml. dry tetrahydrofuran. After 2 hours at room temperature, the solvent is removed and 20 ml. of water is added to the residue. The resultant aqueous mixture is extracted with ether and the extracts washed with water, dried over magnesium sulfate and evaporated to yield 1,3-bis(benzylthio)-2-propanol. obtained by mixing 2.7 g the solvent is removed of water is added to the residue The resultant aqueous mixture is extracted with ether the extracts washed with water dried over magnesium sulfate evaporated

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

実験手順: A mixture of (3S,4S)-3-{N-(3-phenylpropionoyl)-L-phenylalanyl}amino-4-acetoxy-azetidin-2-one (1.67 g, 3.95 mmole), 1,3-dibromo-2-propanol (689 mg, 3.16 mmole), and zinc acetate dihydrate (435 mg, 1.98 mmole) in a mixture of benzene (25 ml) and toluene (25 ml) was refluxed overnight using Dean-Stark water separator. After cooling, the reaction mixture was partitioned between ethyl acetate (200 ml), acetone (40 ml) and water (150 ml). The organic layer was washed with water, brine and dried over sodium sulfate. After removal of the solvent, the residue was purified by silica gel column chromatography using ethyl acetate-hexane (4:3) as eluent and (3S,4S)-3-{N-(3-phenylpropionoyl)-L-phenylalanyl}amino-4-(1,3-dibromoprop-2-yl)oxy-azetidin-2-one was obtained (170 mg, 7% yield). was refluxed overnight After cooling the reaction mixture was partitioned between ethyl acetate (200 ml), acetone (40 ml) and water (150 ml) The organic layer was washed with water, brine dried over sodium sulfate After removal of the solvent the residue was purified by silica gel column chromatography

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

実験手順: 22.0 g of 7,7,8,9,9-pentamethyl-1,3,8-triazaspiro[4.5]decane-2,4-dione and 5.1 g of potassium hydroxide were added to 200 ml of N,N-dimethylformamide, and the mixture was heated, with stirring, for 30 minutes at 50°-60° C. At the end of this time, 9.0 g of 1,3-dibromo-2-propanol were added dropwise to the mixture and the whole mixture was heated, with stirring, for 6 hours at 100°-110° C. After completion of the reaction, the reaction mixture was condensed by evaporation and the residue was washed with a 1% w/w aqueous solution of potassium hydroxide and then recrystallised from a 2:1 by volume mixture of benzene and ethanol, giving the desired Compound No. 164 in the form of white crystals, melting point 255°-256° C. the mixture was heated the whole mixture was heated with stirring, for 6 hours at 100°-110° C After completion of the reaction condensed by evaporation the residue was washed with a 1% w/w aqueous solution of potassium hydroxide recrystallised from a 2:1 by volume mixture of benzene and ethanol

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

実験手順: To a solution of 1,3-dibromo-2-propanol (20.00 g, 91.79 mmol) in methylene chloride (DCM) (100 mL) cooled to 0° C. was added 1H-imidazole (6.56 g, 96.4 mmol) followed by tert-butylchlorodiphenylsilane (25.1 mL, 96.4 mmol) and 4-dimethylaminopyridine (1.12 g, 9.18 mmol). The reaction was stirred with warming to room temperature overnight. The reaction mixture was diluted with diethyl ether, washed with water, and the aqueous layer was again extracted once with ether. The combined organic extracts were washed with water, followed by brine, dried over sodium sulfate, decanted and concentrated. Flash chromatography (eluting with a gradient from 0-15% ethyl acetate/hexanes) afforded desired product (42 g, 100%). 1H NMR (300 MHz, CDCl3): δ 7.72-7.66 (m, 4H), 7.51-7.37 (m, 6H), 4.00-3.91 (m, 1H), 3.49-3.45 (m, 4H), 1.09 (s, 9H). washed with water the aqueous layer was again extracted once with ether The combined organic extracts were washed with water dried over sodium sulfate decanted concentrated Flash chromatography (eluting with a gradient from 0-15% ethyl acetate/hexanes)

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

実験手順: 1,3-Dibromo-2-propanol, dimethoxymethane, and boron trifluoride diethyl ether complex were reacted in methylene chloride at room temperature to obtain 1,3-dibromo-2-(methoxymethoxy)propane.

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

実験手順: 1,3-Dibromo-2-propanol (1.70 ml, 16.5 mmol) and sodium carbonate (15.9 g, 150 mmol) were added to an ethanol (300 ml) solution of tert-butyl(trans-4-aminocyclohexyl)carbamate (3.21 g, 15.0 mmol) and the resulting mixture was stirred under heating to reflux overnight. After cooling, insoluble matter was removed by filtration through celite and then the filtrate was concentrated under reduced pressure. The residue was diluted with water, followed by extraction with ethyl acetate. Then the organic layer was washed with brine. The organic layer was dried over anhydrous sodium sulfate and then the solvent was evaporated under reduced pressure. The residue was dissolved in N,N-dimethylformamide (15 ml) and imidazole (2.45 g, 36.0 mmol) and tert-butyldiphenylchlorosilane (4.29 ml, 16.5 mmol) were added under ice cooling. After stirring at room temperature for 1 hour, the reaction mixture was diluted with ethyl acetate and washed with water and brine in that order. The organic layer was dried over anhydrous magnesium sulfate, then the solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography [chloroform:methanol=10:0→10:1 (v/v)] to give 2.45 g (32%) of the title compound as a colorless solid. under heating to reflux overnight After cooling insoluble matter was removed by filtration through celite the filtrate was concentrated under reduced pressure The residue was diluted with water followed by extraction with ethyl acetate Then the organic layer was washed with brine The organic layer was dried over anhydrous sodium sulfate the solvent was evaporated under reduced pressure The residue was dissolved in N,N-dimethylformamide (15 ml) After stirring at room temperature for 1 hour washed with water and brine in that order The organic layer was dried over anhydrous magnesium sulfate the solvent was evaporated under reduced pressure the residue was purified by silica gel column chromatography [chloroform:methanol=10:0→10:1 (v/v)]

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

実験手順: 1,3-Dibromo-2-propanol (1.70 ml, 16.5 mmol) and sodium carbonate (15.9 g, 150 mmol) were added to an ethanol (300 ml) solution of tert-butyl(trans-4-aminocyclohexyl)carbamate (3.21 g, 15.0 mmol) and the resulting mixture was stirred under heating to reflux overnight. After cooling, insoluble matter was removed by filtration through celite and then the filtrate was concentrated under reduced pressure. The residue was diluted with water, followed by extraction with ethyl acetate. Then the organic layer was washed with brine. The organic layer was dried over anhydrous sodium sulfate and then the solvent was evaporated under reduced pressure. The residue was dissolved in N,N-dimethylformamide (15 ml) and imidazole (2.45 g, 36.0 mmol) and tert-butyldiphenylchlorosilane (4.29 ml, 16.5 mmol) were added under ice cooling. After stirring at room temperature for 1 hour, the reaction mixture was diluted with ethyl acetate and washed with water and brine in that order. The organic layer was dried over anhydrous magnesium sulfate, then the solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography [chloroform:methanol=10:0→10:1 (v/v)] to give 2.45 g (32%) of the title compound as a colorless solid. under heating to reflux overnight After cooling insoluble matter was removed by filtration through celite the filtrate was concentrated under reduced pressure The residue was diluted with water followed by extraction with ethyl acetate Then the organic layer was washed with brine The organic layer was dried over anhydrous sodium sulfate the solvent was evaporated under reduced pressure The residue was dissolved in N,N-dimethylformamide (15 ml) After stirring at room temperature for 1 hour washed with water and brine in that order The organic layer was dried over anhydrous magnesium sulfate the solvent was evaporated under reduced pressure the residue was purified by silica gel column chromatography [chloroform:methanol=10:0→10:1 (v/v)]

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

実験手順: 1,3-dibromo-2-propanol (2.18 g.) is added to a stirred suspension of the salt obtained by mixing 2.7 g. benzyl mercaptan and sodium hydride (56% dispersion in mineral oil; 900 mg.) in 50 ml. dry tetrahydrofuran. After 2 hours at room temperature, the solvent is removed and 20 ml. of water is added to the residue. The resultant aqueous mixture is extracted with ether and the extracts washed with water, dried over magnesium sulfate and evaporated to yield 1,3-bis(benzylthio)-2-propanol. obtained by mixing 2.7 g the solvent is removed of water is added to the residue The resultant aqueous mixture is extracted with ether the extracts washed with water dried over magnesium sulfate evaporated

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

実験手順: 26.7 g (122.4 mmol) of 1,3-dibromopropan-2-ol are dissolved in 150 ml of DCM, and 18.35 g (269.59 mmol) of imidazole are added. 18.47 g (122.54 mmol) of tert-butyldimethylchlorosilane in 150 ml of DCM are subsequently added dropwise. The mixture is left to stir at RT for 18 h, subjected to conventional work-up, giving, as crude product, 39.1 g (Y=95.9%) of step 1 as colourless oil, which is employed directly in step 2. The mixture is left giving, as crude product, 39.1 g (Y=95.9%) of step 1 as colourless oil, which

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

実験手順: 26.7 g (122.4 mmol) of 1,3-dibromopropan-2-ol are dissolved in 150 ml of DCM, and 18.35 g (269.59 mmol) of imidazole are added. 18.47 g (122.54 mmol) of tert-butyldimethylchlorosilane in 150 ml of DCM are subsequently added dropwise. The mixture is left to stir at RT for 18 h, subjected to conventional work-up, giving, as crude product, 39.1 g (Y=95.9%) of step 1 as colourless oil, which is employed directly in step 2. The mixture is left giving, as crude product, 39.1 g (Y=95.9%) of step 1 as colourless oil, which