Chloromethyl Methyl Ether → 4-Methoxymethyltetrahydropyran-4-carboxylic acid methyl ester

Temperature

-10 °C

Into a solution of 3.0 g (20.8 mmol) of tetrahydropyran-4-carboxylic acid methyl ester (IX-49) in tetrahydrofuran (60 mL) was dropped, at −78° C. under an atmosphere of argon, 12.6 mL (25.2 mmol) of 2 mol/L lithium diisopropylamide in hexane-heptane-ethylbenzene (available from Aldrich), and stirred for 90 minutes. To this solution, 1.84 g (22.9 mmol) of chloromethyl methyl ether was added at −78° C., stirred for 30 minutes, and allowed to warm to −10° C. gradually. Saturated aqueous ammonium chloride solution (30 mL) was added to the reaction mixture and stirred for 10 minutes. Then, the reaction mixture was concentrated under a reduced pressure to about one third of its volume, and the residue was extracted with ethyl acetate. The organic layer was washed with water (twice) and saturated brine successively and dried over anhydrous magnesium sulfate, and the solvent was removed. The obtained residue was purified by medium pressure liquid column chromatography on silica gel (developing solvent: hexane-ethyl acetate) to obtain 1.28 g (yield 32.4%) of 4-methoxymethyltetrahydropyran-4-carboxylic acid methyl ester (IX-168) as colorless liquid. Its physical property is shown below.

1. stirringstirred for 10 minutes
2. concentrationThen, the reaction mixture was concentrated under a reduced pressure to about one third of its volume
3. extractionthe residue was extracted with ethyl acetate
4. washThe organic layer was washed with water (twice) and saturated brine successively
5. dry with materialdried over anhydrous magnesium sulfate
6. customthe solvent was removed
7. customThe obtained residue was purified by medium pressure liquid column chromatography on silica gel (developing solvent: hexane-ethyl acetate)

ORD record

ord-03531cd306ad45e69b8c314f83c9520d

Source dataset

uspto-grants-2009_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07511144B2