Ethyl Acetate → Tert-butyl 4-amino-3-chloro-2-fluorobenzoate

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Reaction Steps

To a solution of N-chlorosuccinimide (950 mg, 7.1 mmol) in N,N-dimethylformamide (25 mL) was added dropwise a solution of tert-butyl 4-amino-2-fluorobenzoate (1.5 g, 7.1 mmol) in N,N-dimethylformamide (22 mL). The resulting mixture was stirred at room temperature for 3 hours and then brine solution (80 mL) and ethyl acetate (100 mL) were added. The organic phase was collected and washed three times with brine (50 mL). Combined organic phases were dried on magnesium sulphate and evaporated under reduced pressure. Purification of the residue via silica gel column chromatography (4% EtOAc in iso-hexane) gave tert-butyl 4-amino-5-chloro-2-fluorobenzoate (400 mg, 23%, 1H NMR (400 MHz, DMSO-d6): δ 7.63 (d, J=7.6 Hz, 1H), 6.55 (d, J=13.2 Hz, 1H), 6.46 (brs, 2H), 1.52 (s, 9H)) and tert-butyl 4-amino-3-chloro-2-fluorobenzoate (490 mg, 28%, 1H NMR (400 MHz, DMSO-d6): δ 7.52 (t, J=8.4 Hz, 1H), 6.64 (dd, J=1.2 Hz and J=8.4 Hz, 1H), 6.50 (brs, 2H), 1.53 (s, 9H)) both as a white solid.

Provenance & Evidence