反应详情

温度

-20 °C

To a stirring solution of the diisopropylamine (0.230 mL, 1.617 mmol) in 2.5 mL of THF at −60° C. was added 2.5 M n-butyl lithium in hexanes (0.657 mL, 1.644 mmol) dropwise. The solution was allowed to stir with a gradual warm up to about −20° C. This freshly generated LDA solution was slowly added to a stirring solution of the 6-vinyl-3,4-dihydronaphthalen-1(2H)-one oxime (Intermediate 1, 0.151 g, 0.808 mmol) in 1 mL of THF at ice bath temperature and the reaction mixture was stirred at this temperature for 15 min. To this mixture was then slowly added a solution of ethyl 3-(1-(4-fluorophenyl)cyclohexyl)propanoate (Intermediate 7, 0.15 g, 0.539 mmol) in 2 ml of THF. The reaction was warmed to room temperature and stirred for 4 hrs. It was quenched with saturated aq ammonium chloride and partitioned between ethyl acetate and water. The organic layer was then dried over anhyd. magnesium sulfate, concentrated and dried in vacuo. The residue was taken in 3 ml of toluene and treated with p-toluenesulfonic acid monohydrate (0.205 g, 1.078 mmol) and the mixture was then heated at 60° C. for slightly over an hour. The reaction mixture was cooled and diluted with ethyl acetate and washed with saturated. aq. sodium bicarbonate and brine. It was dried over anhyd. magnesium sulfate, concentrated and chromatographed (40 g REDISEP® silica cartridge; eluted with 10% ethyl acetate-hexanes) to yield 3-(2-(1-(4-fluorophenyl)cyclohexyl)ethyl)-7-vinyl-4,5-dihydronaphtho[1,2-c]isoxazole (89.8 mg, 0.224 mmol, 41.5% yield) as a pale oil. LC/MS M+1=402.22.

1. stirringthe reaction mixture was stirred at this temperature for 15 min
2. temperatureThe reaction was warmed to room temperature
3. stirringstirred for 4 hrs
4. customIt was quenched with saturated aq ammonium chloride
5. custompartitioned between ethyl acetate and water
6. customThe organic layer was then dried over anhyd
7. concentrationmagnesium sulfate, concentrated
8. customdried in vacuo
9. temperaturethe mixture was then heated at 60° C. for slightly over an hour
10. temperatureThe reaction mixture was cooled
11. washwashed with saturated
12. customIt was dried over anhyd
13. concentrationmagnesium sulfate, concentrated
14. customchromatographed
15. wash(40 g REDISEP® silica cartridge; eluted with 10% ethyl acetate-hexanes)