Oxygen → 3-Cyano-4-fluorobenzoic acid

Temperature

0 °C

To a solution of 3-cyano-4-fluorobenzaldehyde (45 g, 301 mmol) in CH3CN (450 mL) was added potassium phosphate monobasic (24 g, 176 mmol) in water (225 mL) and 30% hydrogen peroxide in water (30 mL). The reaction mixture was cooled to 0° C. and sodium chlorite (60 g, 663 mmol) in water (450 mL) was added dropwise over 2 h. The resulting yellow suspension was stirred at room temperature until production of oxygen ceased (4 h). Sodium sulfite (30 g, 238 mmol) in water (100 mL) was added and the reaction mixture stirred for 1 h. The reaction was quenched with 2N HCl (500 mL) and the resulting solid was filtered and washed with water. The aqueous phase was extracted with EA (2×500 mL). The combined organic layers were washed with brine (200 mL), dried over MgSO4, concentrated, and combined with the collected solid to produce a total of 48.5 g (97%) of crude 3-cyano-4-fluorobenzoic acid as a white solid. LCMS-ESI (m/z) calculated for C8H4FNO2: 165.0; found 166.1 [M+H]+, tR=2.54 min. 1H NMR (400 MHz, DMSO) δ 13.60 (s, 1H), 8.41 (dd, J=6.3, 2.1 Hz, 1H), 8.30 (ddd, J=8.8, 5.3, 2.2 Hz, 1H), 7.66 (t, J=9.0 Hz, 1H).

1. custom(4 h)
2. customThe reaction was quenched with 2N HCl (500 mL)
3. filtrationthe resulting solid was filtered
4. washwashed with water
5. extractionThe aqueous phase was extracted with EA (2×500 mL)
6. washThe combined organic layers were washed with brine (200 mL)
7. dry with materialdried over MgSO4
8. concentrationconcentrated

ORD record

ord-5d1ed51bbbda4612a692875fb59fb8b0

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08507538B2