Synthesis
GENERAL STEPS: To a Parr hydrogenation kettle was added PtO2 catalyst and (R)-1-(4-benzyloxy-3-nitrophenyl)-2-bromoethanol (3.60 g, 10.22 mmol) dissolved in a mixture of solvents THF (25 mL) and toluene (25 mL). The reaction was shaken at room temperature and 55 psi pressure for 14 h under hydrogen atmosphere. Upon completion of the reaction, the hydrogen pressure was released. A mixture of formic acid (0.65 mL, 17.23 mmol) and acetic anhydride (1.10 mL, 11.65 mmol) was added directly to the reaction mixture. The newly formed mixture was continued to be stirred at room temperature for 16 hours. At the end of the reaction, the catalyst was removed by filtration through a diatomaceous earth pad and the filtrate was concentrated by rotary evaporation. The resulting residue was purified by column chromatography (silica gel as stationary phase, eluent 30:70 to 50:50 gradient of ethyl acetate/hexane) to afford the target product (R)-N-(2-(benzyloxy)-5-(2-bromo-1-hydroxyethyl)phenyl)formamide (5) as a white solid (3.62 g, yield >99%). The structure of the product was confirmed by 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).
References
[1] Patent: WO2007/146867, 2007, A2. Location in patent: Page/Page column 51-52
[2] Patent: US2011/275623, 2011, A1. Location in patent: Page/Page column 27
