p-Toluenesulfonic acid → 4,6-dichloro-3-(4-(trifluoromethyl)benzyl)-3H-imidazo[4,5-c]pyridine

温度

0 °C

4,6-dichloro-3H-imidazo[4,5-c]pyridine (500 mg, 2.6 mmol), PPh3 (762 mg, 2.91 mmol) and THF (20 mL) were combined and stirred under a nitrogen atmosphere. A solution of 4-trifluoromethyl benzyl alcohol (513 mg, 2.91 mmol) in THF (5 mL) was added at rt. The reaction mixture was cooled to 0° C., and diisopropyl azodicarboxylate (587 mg, 2.91 mmol) was added dropwise. The reaction was warmed to rt and stirred overnight under N2. The reaction was then diluted with EtOAc, washed with brine, dried over Na2SO4, filtered, and concentrated. The crude residue was dissolved in EtOAc (20 ml), p-toluenesulfonic acid (500 mg, 2.91 mmol) was added at rt, and the mixture was stirred for 3 h. The precipitate which formed was collected by filtration and rinsed with EtOAc. The collected precipitate was slurried in EtOAc (50 mL) and was stirred vigorously with aqueous sat'd NaHCO3 (5 mL) for 30 min. The organic layer was separated, and the aqueous layer was extracted several times with EtOAc. The combined organic layers were dried over Na2SO4, filtered, and concentrated. The crude product was purified by silica gel chromatography with 20% to 100% EtOAc/hexanes to obtain the desired isomer, 4,6-dichloro-3-(4-(trifluoromethyl)benzyl)-3H-imidazo[4,5-c]pyridine. 1H NMR (400 MHz, CDCl3): δ8.85 (s, 1H); 7.96 (s, 1H); 7.71 (d, J=8.0 Hz, 2H), 7.33 (d, J=8.0 Hz, 2H), 5.89 (s, 2H). MS APCl calc'd. for C14H8Cl2F3N3 [M+H]+ 346, found 346.

1. temperatureThe reaction was warmed to rt
2. stirringstirred overnight under N2
3. washwashed with brine
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated
7. dissolutionThe crude residue was dissolved in EtOAc (20 ml)
8. stirringthe mixture was stirred for 3 h
9. customThe precipitate which formed
10. filtrationwas collected by filtration
11. washrinsed with EtOAc
12. stirringwas stirred vigorously with aqueous sat'd NaHCO3 (5 mL) for 30 min
13. customThe organic layer was separated
14. extractionthe aqueous layer was extracted several times with EtOAc
15. dry with materialThe combined organic layers were dried over Na2SO4
16. filtrationfiltered
17. concentrationconcentrated
18. customThe crude product was purified by silica gel chromatography with 20% to 100% EtOAc/hexanes

ORDレコード

ord-b1315f3f871a496ba5c084e682d442ba

出典データセット

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08846657B2