tert-Butanol → tert-Butyl (3-chloro-2,6-difluorophenyl)carbamate

Temperature

0 °C

3-chloro-2,6-difluorobenzoic acid (4.85 g, 25.2 mmol) was dissolved in THF (50 mL) and cooled to 0° C. To this solution was then added ethylchloroformate (3.01 g, 27.7 mmol) followed by TEA (3.86 mL, 27.7 mmol) and stirred at the same temperature for 1 h. To the slurry that developed was then added NaN3 in H2O (5 mL) dropwise and stirred the reaction mixture at 0° C. for 1.25 h. Solids separated out from the reaction mixture and allowed the solids to decant followed by separation of the decantant. The residue was dissolved in H2O (50 mL) and extracted with DCM (2×). The above organic layer was then combined with the decantant, dried (MgSO4) and concentrated to yield a residue. The residue was re-dissolved in toluene (50 mL) and heated at 110° C. To the above solution was added t-BuOH (1.5 g) and refluxed for overnight. The reaction mixture was concentrated and purified by silica gel chromatography to yield the desired product (2.86 g, 43%). MS(ESI) m/z: 286.0 (M+Na)+. 1H NMR (400 MHz, CDCl3) δ 7.28 (s, 1H), 7.03-6.72 (m, 1H), 6.10-5.83 (m, 1H), 1.57-1.37 (m, 9H) ppm.

1. customSolids separated out from the reaction mixture
2. customto decant
3. customfollowed by separation of the decantant
4. dissolutionThe residue was dissolved in H2O (50 mL)
5. extractionextracted with DCM (2×)
6. dry with materialdried (MgSO4)
7. concentrationconcentrated
8. customto yield a residue
9. temperatureheated at 110° C
10. temperaturerefluxed for overnight
11. concentrationThe reaction mixture was concentrated
12. custompurified by silica gel chromatography

ORD record

ord-2eaa4c08d0b34c9eac3db4a505510430

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09221818B2