反应详情

Trifluoroacetic acid (6 μL, 78 μmol) was added to 2-(3,5-Dichlorophenyl)-3,3,3-trifluoroprop-1-en-1-yl methyl sulfone (500 mg, 1.57 mmol) in toluene (3 mL). N-Benzyl-1-methoxy-N-[(trimethylsilyl)methyl]methanamine (558 mg, 2.35 mmol) in toluene (2 mL) was added at room temperature over 10 minutes. The reaction mixture was stirred for two hours and then additional N-Benzyl-1-methoxy-N-[(trimethylsilyl)methyl]methanamine (74.4 mg, 313 μmol) was added. The reaction mixture was stirred for additional two hours and then left standing over night. Water was added and after stirring for a while the phases were separated and the aqueous phase was extracted with toluene. The combined organic phases were dried over sodium sulfate and evaporated. The crude product is taken up in warm iso-propanol (1 mL) and 10% hydrochloric acid (0.5 mL) and a drop of methanol was added. The formed crystals were filtered off. The hydrochloride was suspended in water and sodium hydroxide and tert-buthyl methylether was added. The organic phase was separated and the aqueous phase was extracted with tert-buthyl methylether. The combined organic phases were dried over sodium sulfate, filtered and evaporated. This procedure yielded 1-benzyl-3-(3,5-dichlorophenyl)-4-(methylsulfonyl)-3-(trifluoromethyl)pyrrolidine (302 mg, 99% purity, 42% yield).

1. stirringThe reaction mixture was stirred for additional two hours
2. waitleft
3. waitstanding over night
4. stirringafter stirring for a while the phases
5. customwere separated
6. extractionthe aqueous phase was extracted with toluene
7. dry with materialThe combined organic phases were dried over sodium sulfate
8. customevaporated
9. addition10% hydrochloric acid (0.5 mL) and a drop of methanol was added
10. filtrationThe formed crystals were filtered off
11. additionsodium hydroxide and tert-buthyl methylether was added
12. customThe organic phase was separated
13. extractionthe aqueous phase was extracted with tert-buthyl methylether
14. dry with materialThe combined organic phases were dried over sodium sulfate
15. filtrationfiltered
16. customevaporated