Hydrochloric Acid → Ethyl (4-bromo-2-methylphenyl)(oxo)acetate

Participants

Reaction Steps

To a suspension of NaBH4 (5.56 g, 147 mmol) in THF (100 mL) was added dropwise trifluoroacetic acid (16.7 g, 147 mmol) at a rate which maintained the reaction temperature between 25 and 35° C., and the resulting slurry was stirred at room temperature for 30 minutes. To the trifluoroacetoxyborohydride suspension was added a solution of ethyl (4-bromo-2-methylphenyl)-(methoxyimino)ethanoate (11.0 g, 36.7 mmol) in 20 mL of THF. The resulting light yellow mixture was stirred at reflux for 3.5 h and then at room temperature for 16 h. The excess NaBH4 was neutralized by the careful addition of conc. HCl (pH<3). The pH was adjusted to >9 with 50% aq. NaOH and the alkaline mixture was diluted with water (100 mL). The THF was evaporated and the aq. residue was extracted with CH2Cl2 (3×100 mL). The organic extracts were washed with brine, dried (Na2SO4), filtered, and the CH2Cl2 was removed in vacuo to give crude product as a yellow oil. The oil was dissolved in CH2Cl2 and anhydrous HCl was bubbled into the solution. The resulting HCl salt was collected by vacuum filtration and dried to give the desired product as a white solid (5.7 g, 58%). mp 211-214° C. (d); 1H NMR (DMSO-d6) δ 2.35 (s, 3H), 3.67 (d, 2H, J=6.0 Hz), 4.39 (m, 1H), ˜5.30 (bs, 1H), 7.45-7.48 (m, 2H), 7.56 (d, 1H, J=8.8 Hz), 8.66 (s, 3H).

Provenance & Evidence