Toluene → (S)-1-benzyloxy-2-(p-toluenesulfonyloxy)propane

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Reaction Steps

(S)-1-hydroxy-2-tetrahydropyranyloxypropane (120 g, 0.75 mol) prepared according to the method of C. Malanga et al, Synthetic Communications, 12,(1), 67-70 (1982)) was dropwise added to sodium hydride (44.8 g, 1.87 mol) in tetrahydrofuran (400 ml) (hereinafter abbreviated to THF), followed by adding dimethylformamide (hereinafter abbreviated to DMF) (200 ml), agitating the mixture for 2 hours, dropwise adding benzyl bromide (140.8 g, 0.82 mol) at 30° C. or lower, agitating the mixture at room temperature for 6 hours, adding toluene, sufficiently agitating the mixture, washing the resulting organic layer with 2N-NaOH aqueous solution and then with water, drying it over anhydrous magnesium sulfate, distilling off toluene, adding to the resulting oily residue, (S)-1-benzyloxy-2-tetrahydropyranyloxypropane, pyridium p-toluenesulfonate (18 g) and ethanol (500 ml), heating the mixture to 70° C. for one hour, distilling off ethanol, adding toluene to the residue, sufficiently washing it with water, distilling off toluene, and distilling the residue to obtain (S)-1-benzyloxy-2-hydroxypropane (98 g)(b.p. 94.0° C./2.5 mmHg). A mixture of this (S)-1-benzyloxy-2-hydroxypropane (60 g, 0.36 mol) with anhydrous pyridine (300 g) was cooled with ice, followed by dropwise adding a solution of p-toluenesulfonyl chloride (75.8 g, 0.20 mol) in pyridine (70 ml) at 0° C., agitating the mixture at room temperature for 3 hours, adding toluene (800 ml), agitating the mixture, several times washing the resulting organic layer with water, drying it over anhydrous magnesium sulfate and distilling off toluene to obtain (S)-1-benzyloxy-2-(p-toluenesulfonyloxy)propane (115.2 g). On the other hand, a solution of 4-hydroxy-4'-octyloxybiphenyl (50 g, 0.17 mol) in THF (200 ml) was dropwise added to a mixture of sodium hydride (8.5 g, 0.35 mol) with THF (100 ml), followed by dropwise adding a solution of the above (S)-1-benzyloxy-2-(p-toluenesulfonyloxy)propane (64.5 g)(0.20 mol) in DMF (100 ml), agitating the mixture at 60° C. for 4 hours, allowing the mixture to cool down, adding toluene, agitating the mixture, washing with 6N-HCl, then with 2N-NaOH and further with water, drying over anhydrous magnesium sulfate, distilling off toluene, dissolving the residue in a mixture of ethanol (250 ml) with ethyl acetate (250 ml), adding Pd/C catalyst (10 g), agitating the mixture in hydrogen gas, filtering off the Pd/C, distilling off the solvent, and recrystallizing the residue from heptane (150 ml), to obtain (R)-4-(2'-hydroxy-1'-methyl)ethyloxy-4'-octyloxybiphenyl (m.p. 107.9° C.).

Provenance & Evidence