Ethyl bromodifluoroacetate → (4-Amino-3-methyl-5-nitro-phenyl)-difluoro-acetic acid ethyl ester

To a solution of 4-iodo-2-methyl-6-nitroaniline (2.78 g, 10 mmol) and 2-bromo-2,2-difluoroacetic acid ethyl ester (2.03 g, 10 mmol) in anhydrous DMSO (20 mL) was added copper powder (1.28 g, 20 mmol). The mixture was purged with N2 and heated at 60° C. in a sealed vial for 14 h. After being cooled to the room temperature, the reaction mixture was poured into 20% aqueous NH4Cl solution (300 mL). The resulting mixture was basified to pHY=8.5 with saturated aqueous Na2CO3 solution and was extracted with EtOAc (3×100 mL). The organic extract was washed with brine (2×30 mL), dried over Na2SO4 and concentrated. The residue was purified by chromatography (40:1 hexanes/EtOAc) to afford the title compound (1.79 g, 65%). 1H NMR (CDCl3) δ 1.36 (t, 3H), 2.30 (s, 3H), 4.36 (q, 2H), 6.41 (br s, 2H NH), 7.51 (s, 1H), 8.33 (s, 1H). ESI-MS m/z 275 (MH+), 255 (M-F)+, 297 (M+Na)+, 549 (2M+1)+ and 571 (2M+Na)+.

1. customThe mixture was purged with N2
2. temperatureAfter being cooled to the room temperature
3. additionthe reaction mixture was poured into 20% aqueous NH4Cl solution (300 mL)
4. extractionwas extracted with EtOAc (3×100 mL)
5. extractionThe organic extract
6. washwas washed with brine (2×30 mL)
7. dry with materialdried over Na2SO4
8. concentrationconcentrated
9. customThe residue was purified by chromatography (40:1 hexanes/EtOAc)

ORD 기록

ord-51d97dab3a644cb8bf9d3af9708dd9a8

출처 데이터셋

uspto-grants-2014_01

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08629147B2