Water → Carbamic acid, N-[4-bromo-2-(trifluoromethoxy)phenyl]-, phenylmethyl ester

4-Bromo-2-(trifluoromethoxy)aniline (1.0 g, 3.9 mmol) was dissolved in dry toluene (25 mL), sodium carbonate (0.621 g, 5.86 mmol) and benzyl chloroformate (0.669 mL, 4.69 mmol) was added and the mixture stirred under nitrogen at room temperature for 22 hours. The reaction was then heated to 80° C. and stirred at this. temperature for 17 hours and then heated further to reflux and stirred for 22 hours. Water (100 mL) was added to the coiled mixture, the aqueous phase separated and washed with ethyl acetate (2×100 mL). The combined organic extracts were washed with 0.5 M aq. citric acid (70 mL), water (70 mL), brine (70 mL), dried (MgSO4), filtered and concentrated in vacuo to give a pink solid. The crude material was purified by silica gel chromatography (40 g Si cartridge, 0-20% EtOAc in 40-60° C. petroleum benzine) to give the title compound (I46) (1.153 g, 76% yield) as a white solid; 1H NMR (400 MHz, CDCl3) δ 8.15 (d, J=8.7 Hz, 1H), 7.44-7.36 (m, 7H), 6.95 (s, 1H), 5.22 (s, 2H). LCMS Method C: rt 6.67 min; m/z 389.9 [M−H]−.

1. temperatureThe reaction was then heated to 80° C.
2. stirringstirred at this
3. waittemperature for 17 hours
4. temperatureheated further
5. temperatureto reflux
6. stirringstirred for 22 hours
7. customthe aqueous phase separated
8. washwashed with ethyl acetate (2×100 mL)
9. washThe combined organic extracts were washed with 0.5 M aq. citric acid (70 mL), water (70 mL), brine (70 mL)
10. dry with materialdried (MgSO4)
11. filtrationfiltered
12. concentrationconcentrated in vacuo
13. customto give a pink solid
14. customThe crude material was purified by silica gel chromatography (40 g Si cartridge, 0-20% EtOAc in 40-60° C. petroleum benzine)

ORD record

ord-b2d25aec65cf483b8e529cd6771b23ae

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09120761B2