Acetic Acid → 2-[4-(2-Methylquinolin-4-ylmethoxy)benzenesulfonyl]-1-(4-methyltetrahydropyran-4-yl)ethanol

Participants

Reaction Steps

Under an atmosphere of argon, 1.7 mL (3.45 mmol) of 2 mol/L lithium diisopropylamide in hexane-heptane-ethylbenzene was dropped, at −78° C., into a solution of 1.03 g (3.14 mmol) of 4-(4-methanesulfonylphenoxymethyl)-2-methylquinoline (VI-1) in tetrahydrofuran (40 mL), and then stirred for 50 minutes. Into this solution, 3.1 mL (3.10 mmol) of 1 mol/L lithium(bistrimethylsilyl)amide in tetrahydrofuran was dropped at −78° C., and then 745 mg (4.71 mmol) of methyl 4-methyltetrahydropyran-4-carboxylate was dropped and stirred for 6 hours. To the reaction mixture, 471 mg (7.85 mmol) of acetic acid was added, and after stirring for 5 minutes, the reaction mixture was concentrated under a reduced pressure. After the residue was dissolved in ethanol (5 mL), 415 mg (11.0 mmol) of sodium borohydride was added thereto at 0° C. and stirred for 1 hour. Water (15 mL) was added to the reaction mixture, and after stirring for 5 minutes, the reaction mixture was concentrated under a reduced pressure. The residue was extracted by partition between ethyl acetate and water, the organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, and the solvent was removed. The obtained residue was purified by medium pressure column chromatography (developing solvent; hexane-ethyl acetate) to give 1.06 g (yield 74.2%) of 2-[4-(2-methylquinolin-4-ylmethoxy)benzenesulfonyl]-1-(4-methyltetrahydropyran-4-yl)ethanol (VIII-60). Its physical properties are shown below.

Provenance & Evidence