Tetrahydrofuran → 2-[5-(4-{1-[4-(t-Butyl-dimethyl-silanyloxy)-3-methyl-phenyl]-1-ethyl-propyl}-2-methyl-phenyl)-furan-2-yl]-propan-2-ol

Participants

Reaction Steps

A 3 M solution of methylmagnesium bromide in tetrahydrofuran (0.08 mL, 0.24 mmol) was added to a solution of 5-(4-{1-[4-(t-butyl-dimethyl-silanyloxy)-3-methyl-phenyl]-1-ethyl-propyl}-2-methyl-phenyl)-furan-2-carboxylic acid methyl ester (Example 19-(2); 20 mg, 0.039 mmol) in tetrahydrofuran (0.2 mL) at 0° C., and the mixture was stirred at the same temperature for three hours. Ethyl acetate was added to the reaction solution. The organic layer was washed with a sodium bisulfate aqueous solution and brine and dried over anhydrous magnesium sulfate. Then, the solvent was distilled off under reduced pressure to give crude 2-[5-(4-{1-[4-(t-butyl-dimethyl-silanyloxy)-3-methyl-phenyl]-1-ethyl-propyl}-2-methyl-phenyl)-furan-2-yl]-propan-2-ol (8.5 mg). A 1 M solution of tetrabutylammonium fluoride in tetrahydrofuran (0.03 mL, 0.03 mmol) was added to a solution of the resulting compound in tetrahydrofuran (0.2 mL), and the mixture was stirred at room temperature for one minute. Ethyl acetate was added to the reaction mixture. The organic layer was washed with distilled water and brine and then dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. (R)-(−)-Dihydro-5-(p-tolyl-sulfonyloxymethyl)-2(3H)-furanone (11 mg, 0.041 mmol) and potassium carbonate (9 mg, 0.066 mmol) were added to a solution of the residue (6.5 mg) in N,N-dimethylformamide (0.2 mL) at room temperature, and the mixture was stirred at room temperature for 11 hours. Ethyl acetate was added to the reaction solution. The organic layer was washed with brine and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The residue was purified by silica gel chromatography (n-hexane/ethyl acetate=1/1) to give the title compound (2.8 mg, 34.5%).

Provenance & Evidence