Iodine → (2-Fluoro-6-iodophenyl)carbamic acid tert-butyl ester

Temperature

-78 °C

To a cooled (−78° C.) solution of (2-fluoro-phenyl)-carbamic acid tert-butyl ester (38.0 g, 180 mmol) in THF (700 mL) under nitrogen was added tert-butyllithium (1.7 M, 240 mL, 408 mmol). The mixture was stirred for 1 h at −78° C. and then a solution of iodine (60.8 g, 240 mmol) in THF (150 mL) was added slowly. The reaction mixture was stirred for further 1 h. Saturated aqueous ammonium chloride (100 mL) was added slowly and the mixture was warmed to RT. The layers were separated and the aqueous layer was extracted with ethyl acetate (2×100 mL). The combined organic fractions were washed with brine (200 mL), dried over anhydrous sodium sulfate, and concentrated. The residue was purified by flash chromatography (5% ethyl acetate:hexanes) to afford 39.1 g (65%) of the title compound as a while solid. 1H NMR (300 MHz, CDCl3): δ 1.50 (s, 9H), 5.98 (br. s, 1H), 6.92-6.99 (m, 1H), 7.08-7.15 (m, 1H), 7.62 (dt, J=7.8, 1.2 Hz, 1H).

1. stirringThe reaction mixture was stirred for further 1 h
2. temperaturethe mixture was warmed to RT
3. customThe layers were separated
4. extractionthe aqueous layer was extracted with ethyl acetate (2×100 mL)
5. washThe combined organic fractions were washed with brine (200 mL)
6. dry with materialdried over anhydrous sodium sulfate
7. concentrationconcentrated
8. customThe residue was purified by flash chromatography (5% ethyl acetate:hexanes)

ORD record

ord-78adc1bad320480482f5f572c334d041

Source dataset

uspto-grants-2013_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08378104B2