tert-Butanol → Tert-butyl (2-chloro-3-fluoropyridin-4-yl)carbamate

Temperatur

110 °C

To a mixture of 2-chloro-3-fluoroisonicotinic acid (3.55 g, 20.2 mmol) and triethylamine (8.4 mL, 6.13 g, 60.6 mmol) in dry toluene (40 mL) and dry t-BuOH (40 mL) under nitrogen, was added diphenylphosphoryl azide (6.51 mL, 8.27 g, 30.1 mmol). The reaction was heated at 110° C. for 3 hours then cooled to ambient temperature. The reaction mixture was concentrated under reduced pressure. The residue was dissolved in DCM (50 mL) and washed with water (40 mL). The aqueous phase was extracted with DCM (2×40 mL) and the combined organic extract was dried over MgSO4, and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (0-20% EtOAc in DCM) to give the title compound as a yellow oil (3.8 g, 71% yield). 1H NMR (400 MHz, CDCl3): δ 8.09-8.07 (m, 2H), 6.98 (br s, 1H), 1.54 (s, 9H).

1. temperaturethen cooled to ambient temperature
2. concentrationThe reaction mixture was concentrated under reduced pressure
3. dissolutionThe residue was dissolved in DCM (50 mL)
4. washwashed with water (40 mL)
5. extractionThe aqueous phase was extracted with DCM (2×40 mL)
6. extractionthe combined organic extract
7. dry with materialwas dried over MgSO4
8. concentrationconcentrated under reduced pressure
9. customThe residue was purified by silica gel flash chromatography (0-20% EtOAc in DCM)

ORD-Eintrag

ord-aee5abc2284b413b9835ecb229def05e

Quelldatensatz

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08697708B2