Formic Acid → (R)-N-[5-(2-Bromo-1-hydroxyethyl)-2-(phenylmethoxy)phenyl]formamide

Participants

Reaction Steps

A Parr hydrogenator was charged with PtO2 and 1-(4-benzyloxy-3-nitro-phenyl)-2-bromo-1-(R)-ethanol (4) (0.72 g, 2.04 mmol) dissolved in a mixed solvent of THF (8 mL) and toluene (8 mL). The mixture was hydrogenated at 55 psi at rt for 16 h. Then a mixture of formic acid (0.13 mL, 3.45 mmol) and acetic anhydride (0.22 mL, 2.33 mmol) was added and stirring was continued at rt for 66 h. The catalyst was filtered through a Celite pad and the filtrate was concentrated by rotary evaporation. The resulting residue was purified by Biotage silica gel column chromatography eluting with ethyl acetate/dichloromethane (gradient 0% to 10%) to give the desired formamide 5 as a white solid (0.45 g, 63%): 1H NMR (300 MHz, CDCl3) δ 2.95 (s, 1H), 3.52 (m, 1H), 3.60 (m, 1H), 4.85 (m, 1H), 5.08 (s, 2H), 6.96 (d, 1H), 7.13 (dd, 1H), 7.39 (m, 5H), 7.88 (br, 1H), 8.37 (dd, 1H).

Provenance & Evidence