Sulfuric Acid → 6-Fluoro-4-hydroxy-3-methyl-naphthalene-2-carboxylic acid methyl ester
Reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7]([C:12]([OH:14])=[O:13])[C:6]([CH3:15])=[C:5]2[OH:16].S(=O)(=O)(O)O.[C:22](OCC)(=O)C.CCCCCC>CO>[CH3:22][O:13][C:12]([C:7]1[C:6]([CH3:15])=[C:5]([OH:16])[C:4]2[C:9](=[CH:10][CH:11]=[C:2]([F:1])[CH:3]=2)[CH:8]=1)=[O:14]Participants
Procedure
To a 0° C. solution of crude 6-fluoro-4-hydroxy-3-methyl-naphthalene-2-carboxylic acid (28 g, approx. 118 mmol) in MeOH (240 mL) was added concentrated sulfuric acid (18.9 mL, 382 mmol) dropwise. The reaction mixture was then warmed to room temperature and refluxed overnight. After this time, the methanol was distilled off under reduced pressure, and the crude mixture was diluted with ethyl acetate. This solution was washed with saturated aqueous NaHCO3. The organic phase was dried over Na2SO4, filtered and concentrated under reduced pressure to give the crude product. Silica gel column chromatography (6% ethyl acetate-hexane) afforded 6-fluoro-4-hydroxy-3-methyl-naphthalene-2-carboxylic acid methyl ester (14.8 g, 54%) as light yellow solid. MS cald. for C13H12FO3 [(M+H)+] 235, obsd. 235.2.
Workup
- temperaturerefluxed overnight
- distillationAfter this time, the methanol was distilled off under reduced pressure
- additionthe crude mixture was diluted with ethyl acetate
- washThis solution was washed with saturated aqueous NaHCO3
- dry with materialThe organic phase was dried over Na2SO4
- filtrationfiltered
- concentrationconcentrated under reduced pressure
- customto give the crude product
Sources & evidence
- ORD record
- ord-4fbcde60047147ebbb2cb5df02afedbc
- Source dataset
- uspto-grants-2014_04
- Patent number
- US08691993B2
Reaction notes
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