反应详情

The resulting 2-methyl-6-trifluoromethylnicotinic acid (1.026 g, 0.005 mol) is dissolved in 20 ml of oxalyl chloride. Three drops of dimethylformamide are added and the mixture is refluxed for 1 hour. The mixture is then concentrated on a rotary evaporator and the residue (2-methyl-6-trifluoromethylnicotinoyl chloride) is taken up in 100 ml of methylene chloride. At a temperature of 0° C., 1.6 ml (0.0115 mol) of triethylamine and 0.7 g (0.005 mol) of 4,4-dimethylcyclohexane-1,3-dione are added. After 2 hours at a temperature of 22° C., the solvent is removed on a vacuum rotary evaporator, the residue which remains is dissolved in 55 ml of acetonitrile, and 0.15 ml (0.0016 mol) of acetone cyanohydrin and 0.79 ml (0.0057 mol) of triethylamine are added in order to subject the intermediate to a rearrangement reaction. After the reaction solution has been stirred for 4 hours at room temperature, it is evaporated. The syrup which remains is chromatographed on silica gel. Elution with a mixture of toluene, ethyl alcohol, dioxane, triethylamine and water (100:40:20:20:5 parts by volume) gives a pale yellow viscous oil (Rf 0.39 on the abovementioned mixture as mobile phase), which is dissolved in dichloromethane and washed in succession with 75 ml of 5% hydrochloric acid and 75 ml of water. Evaporation to dryness of the organic solution which has been dried with Na2SO4 yields 1.05 g (63%) of pure 3-hydroxy-4,4-dimethyl-2-(2-methyl-6-trifluoromethylpyridine-3-carbonyl)cyclohex-2-enone in the form of white crystals of melting point 75-77° C.

1. temperaturethe mixture is refluxed for 1 hour
2. concentrationThe mixture is then concentrated on a rotary evaporator
3. customthe solvent is removed on a vacuum rotary evaporator
4. dissolutionthe residue which remains is dissolved in 55 ml of acetonitrile
5. customto a rearrangement reaction
6. customit is evaporated
7. customThe syrup which remains is chromatographed on silica gel
8. washElution
9. additionwith a mixture of toluene, ethyl alcohol, dioxane, triethylamine and water (100:40:20:20:5 parts by volume)
10. customgives a pale yellow viscous oil (Rf 0.39 on the abovementioned mixture as mobile phase), which
11. washwashed in succession with 75 ml of 5% hydrochloric acid and 75 ml of water
12. customEvaporation to dryness of the organic solution which
13. dry with materialhas been dried with Na2SO4