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

A Parr hydrogenator was charged with PtO2 and 1-(4-benzyloxy-3-nitro-phenyl)-2-bromo-1-(R)-ethanol (4) (3.60 g, 10.22 mmol) dissolved in a mixed solvent of THF (25 mL) and toluene (25 mL); and the mixture shaken under an atmosphere of hydrogen at 55 psi at rt for 14 h. The hydrogen pressure was then released. To the mixture was added directly a mixture of formic acid (0.65 mL, 17.23 mmol) and acetic anhydride (1.10 mL, 11.65 mmol). The newly resulting mixture was stirred at rt for an additional 16 h. The catalyst was removed by filtration through a Celite pad and the filtrate was concentrated by rotary evaporation. The resulting residue was purified by column chromatography (silica gel, a gradient of 30:70 to 50:50 ethyl acetate/hexanes) to give the desired formamide 5 as a white solid (3.62 g, >99% yield): 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 s, 1H), 8.37 (dd, 1H).

1. additionTo the mixture was added directly
2. customThe newly resulting mixture
3. stirringwas stirred at rt for an additional 16 h
4. customThe catalyst was removed by filtration through a Celite pad
5. concentrationthe filtrate was concentrated by rotary evaporation
6. customThe resulting residue was purified by column chromatography (silica gel

ORD record

ord-583d0287b5c94854acab5dce2270deaf

Source dataset

uspto-grants-2012_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08324218B2