2-Fluoro-4-iodoaniline → (2-Dimethoxymethyl-3-fluoro-5-methoxy-6-nitro-phenyl)-(2-fluoro-4-iodo-phenyl)-amine

To a cold (−78° C.) solution of 2-fluoro-4-iodo-phenyl amine (2.97 g, 12.5 mmol) in THF (20 mL) was added LHMDS (24 mL, 1.0 M solution in hexanes 24 mmol) dropwise maintaining the temperature below −65° C. After stirring for 30 minutes a solution of 2-dimethoxymethyl-1,3-difluoro-5-methoxy-4-nitro-benzene (3.0 g, 11.4 mmol) in THF (20 mL) was added dropwise, the resultant mixture stirred cold (−78° C.) for 1 hour then allowed to warm to room temperature and stirred for 18 hours. The reaction was quenched by the addition of aqueous ammonium chloride and extracted twice with diethyl ether. The combined organic extracts were washed with water, dried (Na2SO4), filtered and concentrated in vacuo to give an orange solid. The crude orange solid was triturated in diethyl ether to give the title compound as a yellow solid (4.2 g, 77%). 1H NMR (CDCl3) 7.36 (1 H, dd, J=10.09, 1.93 Hz), 7.28-7.17 (2 H, m), 6.59 (1 H, t, J=8.62 Hz), 6.44 (1H, d, J=11.47 Hz), 5.49 (1 H, s), 3.88 (3 H, s), 3.39 (6 H, s).

1. temperaturedropwise maintaining the temperature below −65° C
2. additionwas added dropwise
3. customThe reaction was quenched by the addition of aqueous ammonium chloride
4. extractionextracted twice with diethyl ether
5. washThe combined organic extracts were washed with water
6. dry with materialdried (Na2SO4)
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customto give an orange solid
10. customThe crude orange solid was triturated in diethyl ether

ORD record

ord-db06df38e0684729a8126a858fdb9c1e

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08841462B2