Iodine → Ethyl (6-fluoro-3-iodopyridin-2-yl)carbamate

Temperature

-78 °C

28.6 ml (0.18 mol) TMEDA was added to a solution of compound 56 (13.41 g, 72.9 mmol) dissolved in 300 ml anhydrous THF. The mixture was cooled to −78° C. (under N2). To the stirred reaction mixture was added 76 ml (2.5 M n-BuLi) and the mixture was stirred for 2 hours at −78° C. After the addition of I2 (48 g, 0.17 mol), the mixture was stirred for 1 hour at −78° C. The reaction mixture was subsequently quenched with a saturated Na2S2O3 solution and allowed to warm to ambient temperature. Ethyl acetate was added to the mixture and the organic layer was washed with a saturated NaHCO3 solution, dried (Na2SO4), filtered and concentrated. The resulting residue was purified by flash chromatography (diethyl ether/PE (1/3) to 1/1) and afforded (6-fluoro-3-iodo-pyridin-2yl)-carbamic acid ethyl ester (57) (amorphous, 15.86 g, 70%). 1H-NMR (400 MHz, CDCl3): δ 8.07 (bt, J=8 Hz, 1H), 7.24-7.14 (bs, 1H), 6.49 (dd, J=8 Hz, 3 Hz, 1H), 4.29 (q, J=8 Hz, 2H), 1.35 (t, J=8 Hz, 3H). (TLC diethyl ether/PE 1/1 Rf 0.27).

1. customTo the stirred reaction mixture
2. stirringthe mixture was stirred for 1 hour at −78° C
3. customThe reaction mixture was subsequently quenched with a saturated Na2S2O3 solution
4. temperatureto warm to ambient temperature
5. additionEthyl acetate was added to the mixture
6. washthe organic layer was washed with a saturated NaHCO3 solution
7. dry with materialdried (Na2SO4)
8. filtrationfiltered
9. concentrationconcentrated
10. customThe resulting residue was purified by flash chromatography (diethyl ether/PE (1/3) to 1/1)

ORD record

ord-ef59f19c3b594e0e937c46e8b84c0955

Source dataset

uspto-grants-2011_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07964728B2