tert-Butanol → 3-Chloro-2,6-difluoroaniline

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Reaction Steps

To a solution of 3-chloro-2,6-difluorobenzoic acid (500 mg, 2.6 mmol) in DMF (7.5 mL) was added triethylamine (362 μL, 2.6 mmol) and diphenylphosphoryl azide (560 μL, 2.6 mmol). After the mixture was stirred at rt for 1.25 h, 2-methyl-2-propanol (2.5 mL) was added, and the mixture was heated to 90° C. for 2 h. Upon cooling to rt, the solvents were removed in vacuo. The residue was partitioned between water and ethyl acetate. The aqueous was extracted with ethyl acetate. The combined organic extracts were washed with brine, dried over magnesium sulfate, filtered, and concentrated. The residue was purified by flash chromatography (80% hexanes:20% ethyl acetate) yielding 1,1-dimethylethyl (3-chloro-2,6-difluorophenyl)carbamate as a white waxy solid (contaminated with approximately 20% of the aniline). 1H NMR (400 MHz, CDCl3): 7.24 (m, 1H), 6.91 (m, 1H), 5.99 (br s, 1H), 1.51 (s, 9H); GCMS for C11H12ClF2NO2: 263 (M+).

Provenance & Evidence