Benzoyl Peroxide → HCID 86720706, compound

A mixture of methyl 3-fluoro-5-methylbenzoate (1.0 g, 5.95 mmol), N-bromosuccinimide (1.27 g, 7.14 mmol), and dibenzoylperoxide (145 mg, 0.60 mmol) in CHCl3 (50 mL) was heated to reflux for 6 hours. After cooling to room temperature, the reaction mixture was quenched with saturated aqueous NaHCO3 (50 mL), and the layers were separated. The organic phase was washed with saturated aqueous NaHCO3 (50 mL) and then passed through a hydrophobic frit. The solvent was removed in vacuo and the residue was used directly in the next step without any further purification. To the residue was added 2-fluoroaniline (0.23 mL, 2.41 mmol) and potassium carbonate (454 mg, 3.29 mmL) in DMF (5.5 mL). The mixture was stirred at room temperature for 18 hours and then partitioned between EtOAc (30 mL) and water (20 mL). The layers were separated and the aqueous phase extracted with EtOAc (3×30 mL) The combined organic phases were washed with brine (20 mL) and dried over Na2SO4. The mixture was filtered and the solvent was removed in vacuo. The residue was purified on an SCX cartridge washing with MeOH and eluting with 3 to 10% NH3 in DCM. Further purification via silica gel chromatography, eluting with 0-20% EtOAc in isohexane, gave methyl 3-fluoro-5-(((2-fluorophenyl)amino)methyl)benzoate (CD6) as a yellow oil (133 mg, 8.1% over two steps).

1. temperaturewas heated
2. temperatureto reflux for 6 hours
3. customthe reaction mixture was quenched with saturated aqueous NaHCO3 (50 mL)
4. customthe layers were separated
5. washThe organic phase was washed with saturated aqueous NaHCO3 (50 mL)
6. customThe solvent was removed in vacuo
7. customthe residue was used directly in the next step without any further purification
8. custompartitioned between EtOAc (30 mL) and water (20 mL)
9. customThe layers were separated
10. extractionthe aqueous phase extracted with EtOAc (3×30 mL) The combined organic phases
11. washwere washed with brine (20 mL)
12. dry with materialdried over Na2SO4
13. filtrationThe mixture was filtered
14. customthe solvent was removed in vacuo
15. customThe residue was purified on an SCX cartridge
16. washwashing with MeOH
17. washeluting with 3 to 10% NH3 in DCM
18. customFurther purification via silica gel chromatography
19. washeluting with 0-20% EtOAc in isohexane

ORD record

ord-8feaf5dc42ca42f297dc0cd901255493

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09199980B2