Triphenylphosphine → (R)-2-((2-methoxy-4-nitrophenoxy)methyl)oxirane

Participants

Reaction Steps

To a solution of Ph3P (23.3 g; 88.7 mmol) in 450 mL of THF cooled to 0° C. was added a solution of di-t-butylazodicarboxylate (20.4 g; 88.7 mmol) in 50 ml of THF over 15 min. After stirring at 0° C. for 10 min 4-nitroguaiacol (10.0 g; 59.1 mmol) was added followed by (S)-glycidol (6.3 mL; 94.6 mmol) over 10 min and the mixture allowed to warm to rt and stir for 2 h. The solution was concentrated and the residue dissolved in EtOAc, washed with H2O and brine, dried over anhydrous MgSO4, filtered and the filtrate concentrated under reduced pressure. The residue was purified by flash chromatography (silica gel, Hexanes/EtOAc; 100:0 to 1:3 gradient). Impure fractions were concentrated under reduced pressure and the residue further purified by flash chromatography (silica gel, Hexanes/EtOAc; 100:0 to 0:100 gradient). Pure fractions from both purifications were combined and concentrated under reduced pressure to afford 9.58 g (72%) of the title compound as a yellow solid. 1H NMR (CDCl3) δ 2.78-2.80 (m, 1H), 2.94-2.96 (m, 1H), 3.40-3.43 (m, 1H), 3.96 (s, 3H), 4.06-4.11 (m, 1H), 4.41-4.44 (m, 1H), 6.98 (d, J=8.79 Hz, 1H), 7.75 (d, J=2.20 Hz, 1H), 7.89 (dd, J=8.79 Hz, 2.19 Hz, 1H); 13C NMR (CDCl3) δ 28.20, 44.57, 49.75, 56.28, 70.17, 106.80, 111.71, 117.50, 141.92, 149.20, 153.38; HPLC (Method #1) 2.09 min retention time; LCMS (ES): m/z 226 [M+H]+.

Provenance & Evidence