反应详情

温度

0 °C

To the LDA solution was added 6-vinyl-3,4-dihydronaphthalen-1(2H)-one oxime (Intermediate 1, 0.25 g, 1.335 mmol) dissolved in 1 mL of THF dropwise over a period of 1 min. at 0° C. After 15 min., methyl 4-isobutyl-3-(trifluoromethyl)benzoate (Preparation 23B, 0.347 g, 1.335 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. The resulting yellow solid was azeotroped with toluene (5 mL). To the solid was added toluene (5.00 mL), followed by thionyl chloride (0.195 mL, 2.67 mmol) and 1 drop of pyridine. The contents were heated at 110° C. for 5 min. The dark reaction mixture was concentrated and partitioned between ethyl acetate (15 mL) and water (10 mL). The ethyl acetate layer was dried over sodium sulfate, concentrated and subjected to silica gel column chromatography (hexane/ethyl acetate). Fractions corresponding to the product were collected and concentrated to yield 3-(4-isobutyl-3-(trifluoromethyl)phenyl)-7-vinyl-4,5-dihydronaphtho[1,2-c]isoxazole (0.305 g, 0.767 mmol, 57.5% yield) as a pale yellow solid.

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. customThe resulting yellow solid was azeotroped with toluene (5 mL)
7. additionTo the solid was added toluene (5.00 mL)
8. temperatureThe contents were heated at 110° C. for 5 min
9. customThe dark reaction mixture
10. concentrationwas concentrated
11. custompartitioned between ethyl acetate (15 mL) and water (10 mL)
12. dry with materialThe ethyl acetate layer was dried over sodium sulfate
13. concentrationconcentrated
14. customFractions corresponding to the product were collected
15. concentrationconcentrated