反应详情

To a solution of bis(2,2,2-trifluoroethyl)(methoxycarbonylmethyl)phosphonate (0.39 ml, 1.87 mmol) in 5 ml anhydrous tetrahydrofuran was added a solution of 18-crown-6 (2 g, 7.8 mmol) in 5 ml anhydrous tetrahydrofuran. Reaction was cooled to −78° C. to which a 0.5M solution of potassium bis(trimethylsilyl)amide in toluene (0.93 ml, 1.87 mmol) was added all at once. The reaction mixture was stirred at −78° C. for 20 minutes after which a solution of 3-[2-(1H-1-pyrazolyl)acetyl]-benzonitrile (330 mg, 1.56 mmol) in 5 ml anhydrous tetrahydrofuran was added dropwise over several minutes. Reaction was gradually allowed to warm to room temperature and stirred for 5 hours. Reaction was then quenched with a saturated ammonium chloride solution (10 ml) and extracted with 2×25 ml diethyl ether. Combined organic layers were washed with 2×25 ml water, 2×25 ml saturated brine solution, dried over magnesium sulfate, filtered and concentrated to a brown residue. Crude residue was chromatographed on silica gel using a gradient of 5% EtOAc in hexane containing 0.1% triethylamine to 20% EtOAc in hexane containing 0.1% triethylamine to give methyl (E)-3-(3-cyanophenyl)-4-(1H-1-pyrazolyl)-2-butenoate (135 mg, 32%) as a clear oil after drying. H1NMR (CDCl3) 3.521 (s, #H); 4.98 (s, 2H); 5.694 (s, H); 6.237-6.247 (t, H); 7.296-7.593 (m, 6H). NOE experiment confirmed the stereochemical configuration.

1. customReaction
2. additionwas added all at once
3. additionwas added dropwise over several minutes
4. customReaction
5. customReaction
6. customwas then quenched with a saturated ammonium chloride solution (10 ml)
7. extractionextracted with 2×25 ml diethyl ether
8. washCombined organic layers were washed with 2×25 ml water, 2×25 ml saturated brine solution
9. dry with materialdried over magnesium sulfate
10. filtrationfiltered
11. concentrationconcentrated to a brown residue
12. customCrude residue was chromatographed on silica gel using a gradient of 5% EtOAc in hexane containing 0.1% triethylamine to 20% EtOAc in hexane containing 0.1% triethylamine