Hydrochloric Acid → 3-Bromo-2,5-difluoroaniline

A mixture of 1,3-dibromo-2,5-difluorobenzene (4 g, 14.7 mmol), benzophenone imine (2.6 mL, 15.5 mmol), sodium tert-butoxide (2.1 g, 22.1 mmol), (S)-BINAP (1.4 g, 2.2 mmol), in toluene (15 mL) was sparged with Argon and charged with Pd2(dba)3 (0.67 g, 0.74 mmol). The reaction was then sealed and irradiated at 100° C. for 30 minutes in a microwave reactor. The reaction mixture was diluted with Et2O and stirred for 2 hours with a palladium scavenger (Siliabond DMT). The mixture was filtered through a plug of Celite and the collected filtrate was partitioned between diethyl ether and water, and the resulting layers separated. The organic portion was washed with water, brine, dried (MgSO4), and concentrated to afford a brown red solid. The solid was dissolved in THF (40 mL) and treated with aqueous 6.0 N HCl solution (25 ml, 150 mmol). The reaction was stirred for 1.5 hours at room temperature was partitioned between water and Et2O. The layers were separated and the aqueous portion was brought to a pH of 9 with aqueous 1.0 M NaOH solution. The basic aqueous layer was extracted diethyl ether (3×30 mL) the combined diethyl ether layers were washed with aqueous 1.0 M NaOH solution, water, brine, dried (MgSO4), concentrated. Purification by flash chromatography (SiO2, 0-10% EtOAc in heptane) afforded 3-bromo-2,5-difluoroaniline (1.7 g, 8.2 mmol, 56%, trace benzophenone) as an orange solid: 1H NMR (400 MHz, CDCl3) δ 3.93 (br s, 2H) 6.43 (m, 1H) 6.62 (m, 1 H).

1. customin toluene (15 mL) was sparged with Argon
2. customThe reaction was then sealed
3. customirradiated at 100° C. for 30 minutes in a microwave reactor
4. filtrationThe mixture was filtered through a plug of Celite
5. customthe collected filtrate was partitioned between diethyl ether and water
6. customthe resulting layers separated
7. washThe organic portion was washed with water, brine
8. dry with materialdried (MgSO4)
9. concentrationconcentrated
10. customto afford a brown red solid
11. customwas partitioned between water and Et2O
12. customThe layers were separated
13. extractionThe basic aqueous layer was extracted diethyl ether (3×30 mL) the combined diethyl ether layers
14. washwere washed with aqueous 1.0 M NaOH solution, water, brine
15. dry with materialdried (MgSO4)
16. concentrationconcentrated
17. customPurification by flash chromatography (SiO2, 0-10% EtOAc in heptane)

ORDレコード

ord-cd329104887741229f15d985ee6e4880

出典データセット

uspto-grants-2012_08

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08242260B2