Hydrochloric Acid → 2-Phenyl-7-hydroxyquinoline

To a solution of 7-(tert-butyldimethylsilyloxy)quinoline (3.992 g, 15.39 mmol) in dry THF (35 mL), cooled by ice/water, was added phenyllithium (1.8 M in cyclohexane:ether 70:30, 10 mL, 18 mmol). The solution slowly warmed up to ambient temperature and was stirred overnight. More phenyllithium (1.0 mL, 1.8 mmol) was added, and stirring was continued for 4 h. The reaction was quenched by adding saturated NH4Cl solution and water. Most of the THF was evaporated, the residue was extracted with EtOAc (4×30 mL) and the combined EtOAc layers were washed with water (2×) and brine and dried over MgSO4. LC/MS indicated that a significant amount of the TBDMS ether had been cleaved during the workup, the ratio of quinolines to dihydroquinolines was about 1:1. Air was bubbled into the solution overnight, the MgSO4 was filtered off, the filtrate was concentrated, dissolved in MeOH, aq. HCl (2 M, 2 mL, 4 mmol) was added, and the solution was stirred at ambient temperature overnight. Sat. NaHCO3 solution was added, most of the MeOH was evaporated, water (≈100 mL) was added, and the dark brown precipitate was filtered off and washed with more water. The combined filtrate and washings were extracted with EtOAc (4×60 mL), the combined EtOAc extracts were washed with water and brine and dried over MgSO4. The dark brown precipitate was dissolved in MeOH (≈100 mL), the solution was filtered, and the filtrate was adsorbed onto Hydromatrix and chromatographed on silica gel [Jones Flashmaster, 50 g/150 mL cartridge, eluting with CH2Cl2→5% EtOAc in CH2Cl2→10% EtOAc→15% EtOAc]. The mixed fractions were combined with the crude material from the EtOAc extracts and chromatographed on silica gel [Jones Flashmaster, material adsorbed onto Hydromatrix, 10 g/70 mL cartridge, eluting with CH2Cl2→5% EtOAc in CH2Cl2→7.5% EtOAc]. Combination of pure fractions of both columns gave the title compound as light beige solid; 1H NMR (DMSO-d6, 400 MHz) δ 7.15 (dd, J=8.8, 2.4 Hz, 1H), 7.29 (d, J=2.4 Hz, 1H), 7.45-7.51 (m, 1H), 7.51-7.57 (m, 2H), 7.83 (d, J=8.8 Hz, 1H), 7.89 (d, J=8.8 Hz, 1H), 8.20-8.25 (m, 2H), 8.29 (d, J=8.8 Hz, 1H), 10.19 (s, 1H); MS (ES+): m/z 222.1 (100) [MH+]; HPLC: tR=2.2 min (OpenLynx, polar—5 min).

1. stirringstirring
2. waitwas continued for 4 h
3. customThe reaction was quenched
4. additionby adding saturated NH4Cl solution and water
5. customMost of the THF was evaporated
6. extractionthe residue was extracted with EtOAc (4×30 mL)
7. washthe combined EtOAc layers were washed with water (2×) and brine
8. dry with materialdried over MgSO4
9. customAir was bubbled into the solution overnight
10. filtrationthe MgSO4 was filtered off
11. concentrationthe filtrate was concentrated
12. dissolutiondissolved in MeOH
13. stirringthe solution was stirred at ambient temperature overnight
14. customwas evaporated
15. additionwater (≈100 mL) was added
16. filtrationthe dark brown precipitate was filtered off
17. washwashed with more water
18. extractionThe combined filtrate and washings were extracted with EtOAc (4×60 mL)
19. washthe combined EtOAc extracts were washed with water and brine
20. dry with materialdried over MgSO4
21. dissolutionThe dark brown precipitate was dissolved in MeOH (≈100 mL)
22. filtrationthe solution was filtered
23. customchromatographed on silica gel [Jones Flashmaster, 50 g/150 mL cartridge, eluting with CH2Cl2→5% EtOAc in CH2Cl2→10% EtOAc→15% EtOAc]
24. customchromatographed on silica gel [Jones Flashmaster, material adsorbed onto Hydromatrix, 10 g/70 mL cartridge, eluting with CH2Cl2→5% EtOAc in CH2Cl2→7.5% EtOAc]

ORD record

ord-9a685884d3a2491bbdfc9c5a55394029

Source dataset

uspto-grants-2010_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07820662B2