反应详情

A solution of 2-fluoro-3-methoxybenzoic acid (2.50 g, 14.69 mmol) and DIEA (3.07 mL, 17.63 mmol) in a mixture of toluene (12 mL) and t-BuOH (12 mL) was stirred over 4 Å molecular sieves (3 g) for 1 hour at ambient temperature, followed by addition of diphenyl phosphoryl azide (3.9 mL, 17.63 mmol) and the mixture heated at reflux for 18 hours. The cooled reaction mixture was filtered and the filtrate concentrated under reduced pressure. The residue was dissolved in ethyl acetate (50 mL) and washed with 1N HCl solution, saturated sodium bicarbonate solution, water and brine, then dried (MgSO4), filtered and concentrated under reduced pressure. The residue was purified by column chromatography (Biotage 40M; 2.5% ethyl acetate/hexanes) to afford tert-butyl 2-fluoro-3-methoxyphenylcarbamate (2.27 g, 64% Yield).

1. temperaturethe mixture heated
2. temperatureat reflux for 18 hours
3. customThe cooled reaction mixture
4. filtrationwas filtered
5. concentrationthe filtrate concentrated under reduced pressure
6. dissolutionThe residue was dissolved in ethyl acetate (50 mL)
7. washwashed with 1N HCl solution, saturated sodium bicarbonate solution, water and brine
8. dry with materialdried (MgSO4)
9. filtrationfiltered
10. concentrationconcentrated under reduced pressure
11. customThe residue was purified by column chromatography (Biotage 40M; 2.5% ethyl acetate/hexanes)