3-Fluoro-4-formylbenzonitrile → 3-Fluoro-4-hydroxymethylbenzonitrile

To a solution of 3-fluoro-4-formylbenzonitrile (3.6 g, 24.1 mmol) in methanol (40 mL) was added sodium borohydride (0.304 g, 8.04 mmol) slowly at room temperature. After 20 min., the reaction was complete by HPLC and LCMS. The reaction mixture was stirred at room temperature overnight. The reaction was quenched with water (˜5 mL; stirred for 20 min.), and the methanol was removed under reduced pressure. The aqueous residue was diluted with dichloromethane (80 mL), washed with water (50 mL), and collected. The aqueous layer was extracted with dichloromethane (40 mL), and the combined organic layers were dried over anhydrous sodium sulfate. Concentration under reduced pressure afforded 3-fluoro-4-(hydroxymethyl)benzonitrile (3.51 g, 23.2 mmol, 96% yield) as a yellow solid. The compound had an HPLC ret. time=0.720 min.−Column: CHROMOLITH® SpeedROD 4.6×50 mm (4 min.); Solvent A=10% MeOH, 90% H2O, 0.1% TFA; Solvent B=90% MeOH, 10% H2O, 0.1% TFA. MS M+1=152.09. 1H NMR (500 MHz, CDCl3) δ ppm 4.85 (s, 2H), 7.35 (dd, J=9.43, 1.66 Hz, 1H), 7.50 (dd, J=7.91, 1.25 Hz, 1H), and 7.65 (t, J=7.49 Hz, 1H).

1. customThe reaction was quenched with water (˜5 mL; stirred for 20 min.)
2. customthe methanol was removed under reduced pressure
3. additionThe aqueous residue was diluted with dichloromethane (80 mL)
4. washwashed with water (50 mL)
5. customcollected
6. extractionThe aqueous layer was extracted with dichloromethane (40 mL)
7. dry with materialthe combined organic layers were dried over anhydrous sodium sulfate
8. concentrationConcentration under reduced pressure

ORD record

ord-96b25c330b794bb7bd7de8ce8ae5cb8a

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08354398B2