51% |
Stage #1: 1-bromo-4-(trans-4-pentylcyclohexyl)benzene With magnesium In tetrahydrofuran at 80℃; for 1h; Inert atmosphere;
Stage #2: (-)-dimethy-2,3-O-isopropylidene-L-tartrate In tetrahydrofuran at 80℃; for 11.5h; Inert atmosphere; |
1 This example shows an example for synthesizing (4R,5R)-2,2-dimethyl-α,α,α′,α′-tetra[4-(trans-4-n-pentylcyclohexyl)phenyl]-1,3-diox olane-4,5-dimethanol (abbreviation: R-DOL-PC5), which is the dioxolane derivative represented by Structural Formula (100) in Embodiment 1
Into a 100-mL three-necked-flask, 0.33 g (13 mmol) of magnesium was put, and the air in the flask was replaced with nitrogen. Into this flask, 5.0 mL of tetrahydrofuran and several drops of dibromoethane were added, and the mixture was stirred at room temperature. To this mixture, a solution containing 3.9 g (14 mmol) of 1-bromo-4-[trans-4-(n-pentyl)cyclohexyl]benzene in 10 mL of tetrahydrofuran was dropped from a dropping funnel with stirring the mixture. Then, the mixture was further stirred at 80° C. for 1 hour under a nitrogen stream. After a predetermined period, a solution containing 0.61 g (2.8 mmol) of (-)-2,3-O-isopropylidene-L-tartaric acid dimethyl ester in 5.0 mL of tetrahydrofuran was dropped to the mixture from a dropping funnel with stirring the mixture. Then, the mixture was further stirred at 80° C. for 11.5 hours under a nitrogen stream. After a predetermined period, methanol, water, and a dilute hydrochloric acid were added in this order to the mixture, and an aqueous layer was subjected to extraction with toluene. The extracted solution and the organic layer were combined, washed with water, a saturated aqueous solution of sodium hydrogen carbonate, and saturated saline, and dried with magnesium sulfate. [0207] This mixture was separated by gravity filtration, and the obtained filtrate was concentrated to give a yellow oily substance. The oily substance was purified by silica gel column chromatography (developing solvent: toluene). The resulting fraction was concentrated and dried in a vacuum to give a yellow oily substance. This oily substance was purified by high performance liquid column chromatography (HPLC) (developing solvent: chloroform). The resulting fraction was concentrated and dried in a vacuum to give 1.5 g of the target light-yellow solid of R-DOL-PC5 in a yield of 51%. The scheme of the above reactions is shown in (E1-1). This compound was identified as the target R-DOL-PC5 by nuclear magnetic resonance (NMR). [0209] 1H NMR data of the obtained substance, R-DOL-PC5, are as follows. 1H NMR (TCE, 300 MHz): δ (ppm)=0.89-1.46 (m, 82H), 1.80-1.98 (m, 16H), 2.32 (s, 2H), 2.37-2.50 (m, 4H), 4.58 (s, 2H), 7.03-7.40 (m, 16H). [0210] FIGS. 6A and 6B and FIG. 7 show the 1H NMR charts. Note that FIG. 6B is an enlarged chart showing a range of from 0 ppm to 5 ppm of FIG. 6A, and FIG. 7 is an enlarged chart showing a range of from 5 ppm to 10 ppm of FIG. 6A. The measurement results show that R-DOL-PC5, which was the target substance, was obtained. |