3-bromo-4-(oxolan-2-ylmethoxy)aniline

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of ii (3.0 g, 11.62 mmol) in acetic acid (50 mL) was added ammonium thiocynate (4.18 g, 55.11 mmol) at RT. The resulting mixture was stirred at RT for 15 min followed by the addition of bromine (0.68 mL, 13.22 mmol) in acetic acid (5 mL). The mixture was stirred at RT for 5 h. The pH was adjusted to >7 with ammonia solution followed by extraction with EtOAc (2×200 mL). The combined organics were washed with H2O, brine solution, dried (Na2SO4) and concentrated in vacuo. The residue was purified over silica (60% EtOAc-Hexanes) to obtain iii (1.0 g, 26%). 1HNMR (DMSO-d6, 400 MHz): δ 7.50 (s, 1H), 7.49 (s, 1H), 7.43 (br s, 2H), 4.18 (m, 1H), 3.96 (m, 2H), 3.80 (m, 1H), 3.69 (m, 1H), 1.96 (m, 2H) and 1.78 (m, 2H). MS: 329.0 [M+H]+. The mixture was stirred at RT for 5 h followed by extraction with EtOAc (2×200 mL) The combined organics were washed with H2O, brine solution dried (Na2SO4) concentrated in vacuo The residue was purified over silica (60% EtOAc-Hexanes)