p-Bromochlorobenzene → (2R)-4'-chloro-2-(3,4,5,6-tetrahydro-2H-pyran-2-yloxy)propiophenone

To a solution of 1-bromo-4-chlorobenzene (20 g) in tetrahydrofuran (260 ml) was added magnesium (turnings, 7.47 g). The mixture was vigorously stirred at room temperature. When the temperature of the mixture reached 40° C., the reaction vessel was cooled in a water bath. A solution of 1-bromo-4-chlorobenzene (38.9 g) in tetrahydrofuran (90 ml), was added dropwise to the mixture at 34°-40° C., followed by stirring for an hour at 30° C. To the mixture was added dropwise a solution of 4-[(2R)-2-(3,4,5,6-tetrahydro-2H-pyran-2-yloxy)propionyl] morpholine (60 g) in tetrahydrofuran (60 ml) over the period of 15 minutes at 0° C. The mixture was stirred for 3 hours at room temperature. To the reaction mixture were added a saturated aqueous ammonium chloride solution (120 ml) and water (100 ml). The mixture was extracted with ethyl acetate (500 ml). The organic layer was washed with water, dried over magnesium sulfate and distilled under reduced pressure. The residue was purified by silica gel column chromatography (silica gel 900 g, eluent: hexane/ethyl acetate=30:1→10:1) to give (2R)-4'-chloro-2-(3,4,5,6-tetrahydro-2H-pyran-2-yloxy)propiophenone (66 g) as a pale yellow oily substance.

1. customreached 40° C.
2. temperaturethe reaction vessel was cooled in a water bath
3. stirringby stirring for an hour at 30° C
4. stirringThe mixture was stirred for 3 hours at room temperature
5. extractionThe mixture was extracted with ethyl acetate (500 ml)
6. washThe organic layer was washed with water
7. dry with materialdried over magnesium sulfate
8. distillationdistilled under reduced pressure
9. customThe residue was purified by silica gel column chromatography (silica gel 900 g, eluent: hexane/ethyl acetate=30:1→10:1)

ORDレコード

ord-606c6a5fe3514ebdb60a94e7c8be8907

出典データセット

uspto-grants-1994_12

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US05371100