O-Xylene → 5-Fluoroquinoline
Reaction equation
N([O-])=O.[Na+].N[C:6]1[CH:15]=[CH:14][CH:13]=[C:12]2[C:7]=1[CH:8]=[CH:9][CH:10]=[N:11]2.C(OCC)C.C(OCC)(=O)C.C1(C)C(C)=CC=CC=1.[H+].[B-](F)(F)(F)[F:37]>>[F:37][C:6]1[CH:15]=[CH:14][CH:13]=[C:12]2[C:7]=1[CH:8]=[CH:9][CH:10]=[N:11]2Participants
Procedure
Add sodium nitrite in portions to a suspension of 5-aminoquinoline (50 g, 347 mmol) in 48% HBF4 (200 mL) at 0° C. Stir for 1 hour and then pour into 1:1 diethyl ether/ethyl acetate (500 mL). Filter the resulting suspension and dry the solid. Add this solid (82.5 g, 338 mmol) in portions to refluxing xylene (1 L), stir for 2 hours, and then cool. Decant the xylene and dissolve the residue in 1N hydrochloric acid (600 mL). Neutralize with sodium carbonate, extract with ethyl acetate (10×500 mL), dry the extracts over sodium sulfate, filter and concentrate under reduced pressure. Subject the residue to silica gel chromatography, eluting with 10-20% diethyl ether in hexanes. Combine fractions containing product and concentrate them under reduced pressure to provide the desired compound (28.1 g, 55%).
Workup
- filtrationFilter the resulting suspension
- customdry the solid
- stirringstir for 2 hours
- temperaturecool
- customDecant the xylene
- dissolutiondissolve the residue in 1N hydrochloric acid (600 mL)
- extractionNeutralize with sodium carbonate, extract with ethyl acetate (10×500 mL)
- dry with materialdry the extracts over sodium sulfate
- filtrationfilter
- concentrationconcentrate under reduced pressure
- washeluting with 10-20% diethyl ether in hexanes
- additionCombine fractions containing product
- concentrationconcentrate them under reduced pressure
Sources & evidence
- ORD record
- ord-72d3dcfd4c1c4a1f9e3e65009a82c134
- Source dataset
- uspto-grants-2009_02
- Patent number
- US07491716B2
Reaction notes
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