2-Fluorobenzonitrile → 1075715-63-7

Temperature

0 °C

One third of a solution of cyclobutyl bromide (5.0 g, 41.3 mmol) in anhydrous tetrahydrofuran (24 mL) was stirred with magnesium (1.11 g, 46.3 mmol) under reflux. The remaining solution was added dropwise over a period of 15 minutes, and the stirring at reflux continued for 30 min. To the obtained solution 2-fluorobenzonitrile (1.2 g) in THF (15 ml) was added dropwise at 0° C. The mixture was stirred for 5.5 h at 0° C. followed by addition of methanol (30 ml) and sodium borohydride (1.13 g). The reaction mixture was stirred for 16 hours at ambient temperature and concentrated. The residue was partitioned between chloroform (3×100 ml) and water, and the pH was adjusted to 1. The mixture was extracted with chloroform. The aqueous phase was adjusted to pH=10, and extracted with chloroform (3×100 ml). The combined organic layers were dried, evaporated and purified by column chromatography on silica gel (ethyl acetate/petroleum ether=1/1) to afford the title amine (0.45 g, yield: 7.9%) 1H NMR (CD3OD, 400 MHz) 7.49-7.38 (m, 2H), 7.30-7.15 (m, 2H), 4.50 (d, J=10.4 Hz, 1H), 3.00-2.90 (m, 1H), 2.29-2.21 (m, 1H), 2.09-1.71 (m, 5H).

1. temperatureunder reflux
2. additionThe remaining solution was added dropwise over a period of 15 minutes
3. temperaturethe stirring at reflux
4. stirringThe reaction mixture was stirred for 16 hours at ambient temperature
5. concentrationconcentrated
6. customThe residue was partitioned between chloroform (3×100 ml) and water
7. extractionThe mixture was extracted with chloroform
8. extractionextracted with chloroform (3×100 ml)
9. customThe combined organic layers were dried
10. customevaporated
11. custompurified by column chromatography on silica gel (ethyl acetate/petroleum ether=1/1)

ORD record

ord-cbd19f5dc1ec409aa0aba1518ea6b517

Source dataset

uspto-grants-2012_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08207347B2