反应详情

温度

0 °C

8.0 g of 3-bromo-6-propylpyridazine (prepared according to Example 3) were dissolved in 50 ml of triethylamine in a sulphonation flask under nitrogen. The solution was cooled to 0° C., treated with 562 mg of bis-(triphenylphosphine)-palladium (II) dichloride and 76 mg of copper (I) iodide and then treated dropwise within 20 minutes with 7.5 g of trans-1-ethynyl-4-pentylcyclohexane. The mixture was subsequently stirred at 0° C. for several hours, then at room temperature overnight and finally at 50° C. for a further 3 hours. For the working-up, the dark coloured mixture was diluted with 100 ml of tert.butyl methyl ether and suction filtered through a paper filter (rinsing with tert.butyl methyl ether). The filtrate was concentrated on a rotary evaporator. The dark coloured crystalline residue was taken up in 150 ml of tert.butyl methyl ether and washed successively with 100 ml of 2% (wt./vol.) ammonium chloride solution and with 100 ml of water. Each of the aqueous phases were back-extracted with a small amount of tert.butyl methyl ether. The combined organic phases were dried over sodium sulphate and concentrated on a rotary evaporator. For the purification, the brown coloured crystals obtained were chromatographed on silica gel with hexane/ethyl acetate (vol. 2:1), there being obtained a fraction of the desired product 3-[2-(trans-4-pentylcyclohexyl)ethynyl]-6-propylpyridazine (5.2 g) and a mixed fraction consisting of 3-bromo-6-propylpyridazine and product (4.8 g). The pure fraction was recrystallized once from ethanol at -20° C. and once from hexane at -20° C. and finally dried well in a vacuum drying oven at 40° C. There were thus obtained 3.4 g (28.5%) of 3-[2-(trans-4-pentylcyclohexyl)ethynyl]-6-propylpyridazine in the form of white crystals of melting point (C-I) 118.5° C., boiling point 210°-220° C./0.08 Torr.

1. filtrationfiltered through a paper
2. filtrationfilter
3. wash(rinsing with tert.butyl methyl ether)
4. concentrationThe filtrate was concentrated on a rotary evaporator
5. washwashed successively with 100 ml of 2% (wt./vol.) ammonium chloride solution and with 100 ml of water
6. extractionEach of the aqueous phases were back-extracted with a small amount of tert.butyl methyl ether
7. dry with materialThe combined organic phases were dried over sodium sulphate
8. concentrationconcentrated on a rotary evaporator
9. customFor the purification
10. customthe brown coloured crystals obtained
11. customwere chromatographed on silica gel with hexane/ethyl acetate (vol. 2:1), there