The general procedure for the synthesis of 7-fluorobenzodihydropyran-4-one from 3-(3-fluorophenoxy)propionic acid is as follows:
C. Synthesis of 7-fluorobenzodihydropyran-4-one. 3-(3-Fluorophenoxy)propionic acid (2.2 g, 0.011 mol) was dissolved in toluene (25 mL) and thionyl chloride (4.0 mL, 0.054 mol) was added. The reaction mixture was heated to reflux for 1.5 hours and subsequently concentrated under vacuum. The residue was dissolved in chloroform (25 mL), cooled to -65°C and trifluoromethanesulfonic acid (1.5 mL, 0.017 mol) was added dropwise. The mixture was slowly warmed to room temperature and stirring was continued for 2 hours. Upon completion of the reaction, water was added for stratification and the organic layer was washed with 1N NaOH solution. The organic extracts were combined, dried with anhydrous magnesium sulfate, filtered and concentrated, and finally purified by fast column chromatography (eluent: hexane/ethyl acetate) to afford 7-fluorobenzodihydropyran-4-one (0.96 g, 53% yield).
Product Characterization:
HPLC (reversed phase): retention time RT = 8.22 min.
1H NMR (500 MHz, CDCl3): δ 7.92 (dd, J = 8.8, 6.7 Hz, 1H), 6.75-6.72 (m, 1H), 6.66 (dd, J = 9.9, 2.4 Hz, 1H), 4.55 (t, J = 6.4 Hz, 2H), 2.80 (t, J = 6.5 Hz, 2H).
