反应详情

1-(pyrrolidin-1-ylmethyl)-1H-1,2,4-triazole (Preparation 16, 12.0 g, 78.84 mmol) was dissolved in tetrahydrofuran (120 mL) and the solution cooled to −78° C. n-Butyl lithium (2.5M in hexanes, 34.7 ml, 86.7 mmol) was then added dropwise over 30 mins. After warming to room temperature and stirring for 1 hour the reaction mixture was cooled to −78° C. and a solution of cyclohexyl(phenyl)methanone (16.3 g, 86.7 mmol) in tetrahydrofuran (30 mL) added dropwise. After warming to room temperature over 18 hr, water (100 ml) was added and the solvent removed in vacuo. The residue was partitioned with ethyl acetate (200 ml), the aqueous phase separated and re-extracted with ethyl acetate (2×200 ml). The combined organic layers were dried over magnesium sulphate, filtered and the solvent removed in vacuo to furnish the title compound as a yellow oil, in 100% yield, 27.28 g.

1. additionwas then added dropwise over 30 mins
2. temperaturewas cooled to −78° C.
3. temperatureAfter warming to room temperature over 18 hr
4. customthe solvent removed in vacuo
5. customThe residue was partitioned with ethyl acetate (200 ml)
6. customthe aqueous phase separated
7. extractionre-extracted with ethyl acetate (2×200 ml)
8. dry with materialThe combined organic layers were dried over magnesium sulphate
9. filtrationfiltered
10. customthe solvent removed in vacuo