反应详情

Thionyl chloride (3.6 ml) was added to a clear solution of 4′-(trifluoromethyl)-[1,1′-biphenyl]-2-carboxylic acid (0.025 mol) in DMF (1 ml) and DCM (100 ml). The mixture was stirred and refluxed for one hour. The solvent was evaporated. DCM (50 ml) was added to the residue, then evaporated. The residue was dissolved in DCM (50 ml) and the solution was added dropwise to a solution of intermediate (18) (0.025 mol) in DCM (150 ml) and DIPEA (0.049 mol). The reaction mixture was stirred for 2 hours at room temperature. Water was added and this mixture was extracted twice. The separated organic layer was dried, filtered and the solvent evaporated. The residue was stirred in DIPE, filtered off, dried, and crystallized from 2-propanol (150 ml; later, 300 ml was added). The mixture was stirred for 2 hours at room temperature. The precipitate was filtered off, washed with 2-propanol and dried, yielding 8.58 g of methyl α-phenyl-1-[4-[[[4′-(trifluoromethyl)[1,1′-biphenyl]-2-yl]carbonyl]amino]phenyl]-4-piperidineacetate (intermediate 23).

1. temperaturerefluxed for one hour
2. customThe solvent was evaporated
3. additionDCM (50 ml) was added to the residue
4. customevaporated
5. dissolutionThe residue was dissolved in DCM (50 ml)
6. stirringThe reaction mixture was stirred for 2 hours at room temperature
7. extractionthis mixture was extracted twice
8. customThe separated organic layer was dried
9. filtrationfiltered
10. customthe solvent evaporated
11. stirringThe residue was stirred in DIPE
12. filtrationfiltered off
13. customdried
14. customcrystallized from 2-propanol (150 ml
15. additionlater, 300 ml was added)
16. stirringThe mixture was stirred for 2 hours at room temperature
17. filtrationThe precipitate was filtered off
18. washwashed with 2-propanol
19. customdried