反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.
实验步骤: (1R*,4R*,5R*)-4-Iodo-6-oxabicyclo[3.2.1]octan-7-one (2.8 g) was dissolved in a solvent mixture of tetrahydrofuran (27 mL) and water (3 mL), and concentrated HCl (0.1 mL) was added thereto, followed by heating under reflux for 1 hour. The solvent was distilled away under reduced pressure, to thereby give (1R*,3R*,4R*)-3-hydroxy-4-iodocyclohexanecarboxylic acid (3.23 g) as a colorless solid. 2) The product obtained from the above-described reaction (3.22 g) was dissolved in tetrahydrofuran (50 mL), and borane-dimethyl sulfide complex (as 2M tetrahydrofuran solution, 47 mL) was added to the solution under ice cooling, followed by stirring at room temperature for 12 hours. The solvent was distilled away under reduced pressure, and the residue was dissolved in isopropanol (10 mL). To the solution was added 1N aqueous sodium hydroxide (12 mL) at room temperature, and the mixture was stirred for 12 hours. After the mixture was concentrated to about one-fifth of its original volume, the resultant mixture was diluted with water and methylene chloride, followed by stirring for 10 minutes. The organic layer was separated, and was sequentially washed with saturated aqueous ammonium chloride and saturated brine, followed by drying over anhydrous magnesium sulfate. The solvent was distilled away under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:2), to thereby give (1R*,3R*,6S*)-7-oxabicyclo[4.1.0]hept-3-ylmethanol (1.25 g) as a colorless oily matter. 3) The product obtained from the reaction in the above step 2) (4.63 g) was dissolved in tetrahydrofuran (50 mL), and to the solution was added potassium bis(trimethylsilyl)amide (as 0.5N toluene solution, 80 mL) at −78° C., followed by stirring at the same temperature for 10 minutes, and methyl iodide (2.93 mL) was added thereto. The resultant mixture was heated to 0° C., and was stirred for 1 hour. Saturated aqueous ammonium chloride was added to the thus-obtained mixture, and the mixture was diluted with diethyl ether. The organic layer was separated, and was washed with saturated brine, followed by drying over anhydrous magnesium sulfate. The solvent was distilled away under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:4), to thereby give the title compound (3.7 g).
was added
by heating
under reflux for 1 hour
The solvent was distilled away under reduced pressure
2) The product obtained from the above-described reaction (3.22 g)
The solvent was distilled away under reduced pressure
the residue was dissolved in isopropanol (10 mL)
To the solution was added 1N aqueous sodium hydroxide (12 mL) at room temperature
the mixture was stirred for 12 hours
After the mixture was concentrated to about one-fifth of its original volume
the resultant mixture was diluted with water and methylene chloride
by stirring for 10 minutes
The organic layer was separated
was sequentially washed with saturated aqueous ammonium chloride and saturated brine
by drying over anhydrous magnesium sulfate
The solvent was distilled away under reduced pressure
the residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:2)
3) The product obtained from the reaction in the above step 2) (4.63 g)
by stirring at the same temperature for 10 minutes
was stirred for 1 hour
The organic layer was separated
was washed with saturated brine
by drying over anhydrous magnesium sulfate
The solvent was distilled away under reduced pressure
the residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:4)
来源 ID: ord-ab769c3a7c3446989cbb334bd5c3aca7