反应详情

温度

0 °C

To the LDA solution at 0° C. was added 6-vinyl-3,4-dihydronaphthalen-1(2H)-one oxime (Intermediate 1, 0.212 g, 1.132 mmol) as a solution in THF (1 mL), dropwise over a period of 1 min. After 15 min. isopropyl 4-isopropoxy-3-(trifluoromethyl)benzoate (Preparation 14A, 0.329 g, 1.132 mmol) dissolved in 1 mL of THF was added dropwise over a period of 1 min. at 0° C. and the contents were stirred at 0° C. for 10 min. The reaction mixture was partitioned between 1N hydrochloric acid (5 mL) and ethyl acetate (10 mL)-THF. The 1N hydrochloric acid layer was back extracted with ethyl acetate (10 mL). The combined ethyl acetate layers were dried over sodium sulfate and concentrated under reduced pressure to yield a dark oil. To this oil was added toluene (5 mL). The contents were sonicated for 2 min. and p-toluenesulfonic acid monohydrate (0.431 g, 2.265 mmol) was added at room temperature. The contents were heated at 110° C. for 25 min. The reaction mixture was concentrated and partitioned between dichloromethane (15 mL) and sat. aq. sodium bicarbonate (10 mL). The dichloromethane layer was dried over sodium sulfate, concentrated and subjected to silica gel column chromatography (hexane/ethyl acetate). Product fractions were collected and concentrated to yield 3-(4-isopropoxy-3-(trifluoromethyl)phenyl)-7-vinyl-4,5-dihydronaphtho[1,2-c]isoxazole as a semi-solid (180 mg). LC/MS M+1=400.1.

1. additionwas added dropwise over a period of 1 min. at 0° C.
2. customThe reaction mixture was partitioned between 1N hydrochloric acid (5 mL) and ethyl acetate (10 mL)-THF
3. extractionThe 1N hydrochloric acid layer was back extracted with ethyl acetate (10 mL)
4. dry with materialThe combined ethyl acetate layers were dried over sodium sulfate
5. concentrationconcentrated under reduced pressure
6. customto yield a dark oil
7. customThe contents were sonicated for 2 min.
8. temperatureThe contents were heated at 110° C. for 25 min
9. concentrationThe reaction mixture was concentrated
10. custompartitioned between dichloromethane (15 mL) and sat. aq. sodium bicarbonate (10 mL)
11. dry with materialThe dichloromethane layer was dried over sodium sulfate
12. concentrationconcentrated
13. customProduct fractions were collected
14. concentrationconcentrated