Hydrochloric Acid → HCID 22279952, compound

Temperature

0 °C

To a solution of 5-bromo-4-fluoro-2-methylphenylhydrazine hydrochloride (4.75 g, 18.6 mmol) in 20% aqueous THF (100 mL) at 0° C. was added dropwise a solution of 2,3-dihydrofuran (1.55 mL, 20.4 mmol) in THF (10 mL). After stirring for 2 hours at 0° C. and 12 hours at room temperature, the reaction mixture was diluted with ether (100 mL). The organic solution was washed with saturated NaHCO3 (2×100 mL) and brine (100 mL), dried (Na2SO4) and concentrated. The residue was dissolved in ethylene glycol (50 mL), treated with ZnCl2 (5.58 g, 40.9 mmol), and heated at 170° C. for 4 hours. The reaction mixture was cooled down to room temperature and 6 N HCl (100 mL) was added. The mixture was extracted with ether (3×100 mL) and washed with water (200 mL) and brine (200 mL). The organic solution was dried over Na2SO4 and concentrated. The residue was purified by flash chromatography (silica, 40% EtOAc in hexanes) to give 1.52 g (30%) of title compound containing inseparable impurities (<20%) as a light brown oil. 1H NMR (CDCl3): 300 MHz δ 8.68 (bs, 1H), 7.06 (d, J=2.4 Hz, 1H), 6.76 (d, J=9.63 Hz, 1H), 3.92 (t, J=6.48 Hz, 2H), 3.21 (t, J=6.48 Hz, 2H), 2.35 (s, 3H), 2.27 (bs, 1H).

1. washThe organic solution was washed with saturated NaHCO3 (2×100 mL) and brine (100 mL)
2. dry with materialdried (Na2SO4)
3. concentrationconcentrated
4. dissolutionThe residue was dissolved in ethylene glycol (50 mL)
5. temperatureheated at 170° C. for 4 hours
6. temperatureThe reaction mixture was cooled down to room temperature
7. extractionThe mixture was extracted with ether (3×100 mL)
8. washwashed with water (200 mL) and brine (200 mL)
9. dry with materialThe organic solution was dried over Na2SO4
10. concentrationconcentrated
11. customThe residue was purified by flash chromatography (silica, 40% EtOAc in hexanes)

ORD record

ord-ee2ebdd79df34b1da9dea4deee903a8e

Source dataset

uspto-grants-2007_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07217730B2