Sulfuric Acid → HCID 67171654, Verbindung

Temperatur

0 °C

To 6-vinyl-3,4-dihydronaphthalen-1(2H)-one oxime (Intermediate 1, 0.151 g, 0.808 mmol) was added 5 mL of toluene and the contents were concentrated under reduced pressure. The resulting solid was kept under high vacuum for 10 min. The white solid was cooled to 0° C. and lithium diisopropylamide (2.0 M, 0.8 mL, 1.61 mmol) was added drop wise over a period of 3 min. The reaction mixture was stirred at 0° C. for 20 min., then methyl 3-(trifluoromethyl)benzoate (0.087 mL, 0.539 mmol) was added dropwise over a period of 1 min. at 0° C. After 10 min. at 0° C., concentrated sulfuric acid (0.2 mL) was added dropwise at 0° C. and the reaction was stirred for 20 minutes. Water (2 mL) was added and the homogenous solution was heated at 60° C. for ˜2 hr. The reaction mixture was stirred overnight at room temperature. The contents were concentrated under reduced pressure. Next, 5 mL of dioxane was added and the contents were heated at 100° C. for 1.5 hr. The reaction mixture was concentrated under reduced pressure and partitioned between ethyl acetate (20 mL) and sat. aq. sodium bicarbonate (10 mL). The ethyl acetate layer was dried over sodium sulfate, concentrated under reduced pressure, and purified by silica gel column chromatography (hexane/ethyl acetate). Fractions corresponding to the product were collected and concentrated to yield 3-(3-(trifluoromethyl)phenyl)-7-vinyl-4,5-dihydronaphtho[1,2-c]isoxazole (0.15 g, 0.439 mmol, 82% yield) as a pale yellow solid. LC/MS M+1=342.

1. concentrationthe contents were concentrated under reduced pressure
2. waitAfter 10 min. at 0° C.
3. stirringthe reaction was stirred for 20 minutes
4. temperaturethe homogenous solution was heated at 60° C. for ˜2 hr
5. stirringThe reaction mixture was stirred overnight at room temperature
6. concentrationThe contents were concentrated under reduced pressure
7. additionNext, 5 mL of dioxane was added
8. temperaturethe contents were heated at 100° C. for 1.5 hr
9. concentrationThe reaction mixture was concentrated under reduced pressure
10. custompartitioned between ethyl acetate (20 mL) and sat. aq. sodium bicarbonate (10 mL)
11. dry with materialThe ethyl acetate layer was dried over sodium sulfate
12. concentrationconcentrated under reduced pressure
13. custompurified by silica gel column chromatography (hexane/ethyl acetate)
14. customFractions corresponding to the product were collected
15. concentrationconcentrated

ORD-Eintrag

ord-5b6114487ca34a399373d303de1b3cbb

Quelldatensatz

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09216972B2