Thionyl Chloride → 1-(3,3,3-Trifluoro-2-hydroxy-2-methylpropanoylamino)-6,11-dihydrodibenz[b,e]oxepin-11-one

Temperature

-10 °C

In dimethylacetamide (3 ml) was dissolved 3,3,3-trifluoro-2-hydroxy-2-methylpropionic acid (0.17 g, 1.1 mmol), and thionyl chloride (80 μl, 1.1 mmol) was added thereto at -15° C., followed by stirring at -15 to -5° C. for one hour. To this reaction mixture was added 1-amino-6,11-dihydrodibenz[b,e]oxepin-11-one obtained in Reference Example 4 (0.17 g, 0.77 mmol), and the mixture was stirred overnight at room temperature. After concentration of the reaction mixture under reduced pressure, the obtained oily residue was dissolved in ethyl acetate (20 ml). The organic layer was washed successively with a 5% aqueous solution of sodium bicarbonate and a saturated aqueous solution of sodium chloride, and then dried over anhydrous magnesium sulfate. After the drying agent was filtered off, the organic layer was concentrated under reduced pressure. The obtained oily residue was purified by silica gel column chromatography (hexane/ethyl acetate=5/1), followed by trituration with hexane to give Compound 1 (80 mg, 30%).

1. additionwas added
2. customat -15° C.
3. stirringthe mixture was stirred overnight at room temperature
4. washThe organic layer was washed successively with a 5% aqueous solution of sodium bicarbonate
5. dry with materiala saturated aqueous solution of sodium chloride, and then dried over anhydrous magnesium sulfate
6. filtrationAfter the drying agent was filtered off
7. concentrationthe organic layer was concentrated under reduced pressure
8. customThe obtained oily residue was purified by silica gel column chromatography (hexane/ethyl acetate=5/1)

ORD record

ord-45cdb5a182c44dd2b68a1aad0b23d6f4

Source dataset

uspto-grants-1998_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05726325