Sulfuric Acid → 4-Cyclopropyl-2-fluoro-1-iodobenzene

To a stirred mixture of 4-cyclopropyl-2-fluoroaniline (1.63 g, 10.78 mmol) in water (20 mL) at 0° C. was added concentrated sulfuric acid (8.6 mL, 15.0 eq.) dropwise, while keeping the temperature constant at 0° C. A solution of sodium nitrite (781.0 mg, 11.32 mmol, 1.05 eq.) in water (2.7 mL) was added and stirred for 5 minutes. This resulting reaction mixture was then added to a solution of potassium iodide (3.76 g, 22.64 mmol, 2.1 eq.) in water (9.7 mL), and the reaction mixture was stirred at 60° C. for 3 h. DCM (400 mL) was added to the cooled reaction. The biphasic layers were separated, and the aqueous layer was extracted with DCM (2×150 mL). The combined organic layers were washed with saturated aqueous Na2S2O4, water, and brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude residue was purified via flash column chromatography eluted with 100% heptane to give 2.01 g (71.28%) of 4-cyclopropyl-2-fluoro-1-iodobenzene as a clear oil. 1H NMR (400 MHz, CDCl3) δ 7.57 (dd, J=8.0, 6.9 Hz, 1H), 6.76 (dd, J=9.4, 1.9 Hz, 1H), 6.64 (dd, J=8.2, 1.9 Hz, 1H), 1.94-1.77 (m, 1H), 1.09-0.95 (m, 2H), 0.79-0.56 (m, 2H).

1. customconstant at 0° C
2. customThis resulting reaction mixture
3. stirringthe reaction mixture was stirred at 60° C. for 3 h
4. customThe biphasic layers were separated
5. extractionthe aqueous layer was extracted with DCM (2×150 mL)
6. washThe combined organic layers were washed with saturated aqueous Na2S2O4, water, and brine
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. customThe crude residue was purified via flash column chromatography
11. washeluted with 100% heptane

ORD record

ord-ef60e1037b2b482693fd680652bb4f53

Source dataset

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09328106B2