Methanol → HCID 58085876, compound
Reaction equation
[NH2:1][C:2]1[C:10]([OH:11])=[C:9]([F:12])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].S(Cl)(Cl)=O.[CH3:17]O>>[NH2:1][C:2]1[C:10]([OH:11])=[C:9]([F:12])[CH:8]=[CH:7][C:3]=1[C:4]([O:6][CH3:17])=[O:5]Participants
4
Conditions
- Temperature
- -78 °C
Procedure
To a solution of 2-amino-4-fluoro-3-hydroxybenzoic acid (2.44 g, 9.7 mmol) in methanol (200 mL) was added thionyl chloride (3.8 mL, 50 mmol) at −78° C. The mixture was stirred in the boiling solvent for 17 h. The solvent was removed under reduced pressure; the residue was dissolved in methanol (200 mL). The solution was cooled to −78° C. and treated with thionyl chloride (8 mL, 100 mmol). The mixture was stirred in boiling solvent for 48 h. The solvent was removed under reduced pressure and the crude material was purified by column chromatography (silica gel, 0 to 70% ethyl acetate in hexanes) to afford methyl 2-amino-4-fluoro-3-hydroxybenzoate (1.5 g, 44%) as off-white solid. 1H NMR (300 MHz, CDCl3) δ 7.48-7.43 (m, 1H), 6.40 (t, J=9.3 Hz, 1H), 3.87 (s, 3H); MS (ESI+) m/z 186 (M+H).