Potassium Carbonate → tert-Butyl 4-(4-(4-(benzyloxy)-4'-(trifluoromethyl)biphenyl-3-yl)pyridin-2-yl)piperazine-1-carboxylate

온도

130 °C

tert-Butyl 4-(4-(2-(benzyloxy)-5-chlorophenyl)pyridin-2-yl)piperazine-1-carboxylate (Preparation 116, 1.10 g, 2.29 mmol), 4-(trifluoromethyl)phenylboronic acid (866 mg, 4.58 mmol), di-μ-chlorobis[5-chloro-2-[(4-chlorophenyl)(hydroxyimino)methyl]phenyl]palladium (II) dimer (93 mg, 0.114 mmol), tri-tert-butylphosphonium tetrafluoroborate (66 mg, 0.228 mmol), potassium carbonate (635 mg, 4.60 mmol) and tetrabutyl ammonium hydroxide (1M in methanol, 0.46 mL, 0.46 mmol) were combined in a microwave vial. Dimethylformamide (12 mL) was added and the vial was sealed. The mixture was heated at 130° C. for 2 hours in a microwave and then partitioned between ethyl acetate (15 mL) and water (5 mL). The organic layer was separated, washed with brine (5 mL), dried over anhydrous MgSO4, filtered and concentrated in vacuo. The residue was dissolved in dimethylformamide (12 mL) and 4-(trifluoromethyl)phenylboronic acid (866 mg, 4.58 mmol), di-mu-chlorobis[5-chloro-2-[(4-chlorophenyl)(hydroxyimino)methyl]phenyl]palladium (II) dimer (93 mg, 0.114 mmol), tri-tert-butylphosphonium tetrafluoroborate (66 mg, 0.228 mmol), potassium carbonate (635 mg, 4.60 mmol) and tetrabutyl ammonium hydroxyde (1M in methanol, 0.46 mL, 0.46 mmol) were added. The mixture was heated at 130° C. for 1 hour in microwave and then partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and concentrated in vacuo. The oil residue was purified on silica gel by Biotage (5% to 80% ethyl acetate in heptane over 20 CV) to give the title compound as a white solid (655 mg, 48%).

1. customthe vial was sealed
2. custompartitioned between ethyl acetate (15 mL) and water (5 mL)
3. customThe organic layer was separated
4. washwashed with brine (5 mL)
5. dry with materialdried over anhydrous MgSO4
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. dissolutionThe residue was dissolved in dimethylformamide (12 mL)
9. temperatureThe mixture was heated at 130° C. for 1 hour in microwave
10. custompartitioned between ethyl acetate and water
11. washThe organic layer was washed with brine
12. dry with materialdried over anhydrous magnesium sulfate
13. concentrationconcentrated in vacuo
14. customThe oil residue was purified on silica gel by Biotage (5% to 80% ethyl acetate in heptane over 20 CV)

ORD 기록

ord-44921d0daf1c4c45b9360323d6ec6cb1

출처 데이터셋

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08772293B2