反应详情

Into a cooled (−78° C.) solution of 1.00 g (6.32 mmol) of (tetrahydropyran-4-yl)acetic acid methyl ester in tetrahydrofuran (20 mL) was dropped, under an atmosphere of argon, a solution of 4.5 mL (9.00 mmol) of 2 mol/L lithium diisopropylamide in hexane-heptane-ethylbenzene (available from Aldrich) and subsequently 0.47 mL (7.55 mmol) of methyl iodide, and then stirred for 30 minutes at −78° C., followed by stirring for 48 hours at room temperature. After 1N hydrochloric acid was added to the reaction mixture, it was concentrated under a reduced pressure and extracted with ethyl acetate. 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 column chromatography (silica gel 30 g, developing solvent: hexane:ethyl acetate=4: 1) to obtain 927 mg (85.1%) of 2-(tetrahydropyran-4-yl)propionic acid methyl ester (IX-166). Its physical property is shown below.

1. additionwas dropped, under an atmosphere of argon
2. concentrationwas concentrated under a reduced pressure
3. extractionextracted with ethyl acetate
4. washThe organic layer was washed with saturated brine
5. dry with materialdried over anhydrous magnesium sulfate
6. customthe solvent was removed
7. customThe obtained residue was purified by column chromatography (silica gel 30 g, developing solvent: hexane:ethyl acetate=4: 1)