Hydrochloric Acid → Dihydro-8-fluoro-2H-1,4-benzoxazine-2-methanamine

Temperature

60 °C

To a solution of 4b (0.75 g, 3.83 mmol) in anhydrous THF (20 mL) held at ambient temperature in an inert atmosphere, is added dropwise a solution of LiAlH4 in THF (13.4 mL, 13.4 mmol). When addition is completed, the mixture is heated to 60° C. for 11 h. The mixture obtained is cooled to 0° C. then an aqueous solution of hydrochloric acid (1N) is added slowly until a pH of 3 is reached. The mixture is concentrated under reduced pressure then the residue is made alkaline through the addition of an aqueous NaOH solution (1N). The mixture is extracted with ethyl acetate, the organic phase is washed with water then with salt water, dried over MgSO4 and concentrated under reduced pressure. The residue is purified by silica gel chromatography using a dichloromethane-methanol mixture (85:5) as eluting solvent. The title compound is obtained in oil form (1.1 g, 59%).

1. customheld at ambient temperature in an inert atmosphere
2. additionWhen addition
3. customThe mixture obtained
4. temperatureis cooled to 0° C.
5. concentrationThe mixture is concentrated under reduced pressure
6. additionthrough the addition of an aqueous NaOH solution (1N)
7. extractionThe mixture is extracted with ethyl acetate
8. washthe organic phase is washed with water
9. dry with materialwith salt water, dried over MgSO4
10. concentrationconcentrated under reduced pressure
11. customThe residue is purified by silica gel chromatography
12. washas eluting solvent

ORD record

ord-7967db52f6314fd998f64e7ae0ffc837

Source dataset

uspto-grants-2014_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08669250B2