4-Benzylphenol → (R)-2-(4-Benzyl-phenoxymethyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

To a solution of 4-benzylphenol (103 mg, 0.56 mmol) in DMF (1 mL) was added 95% NaH (19 mg, 0.75 mmol) at 0° C., and the resulting mixture was stirred at 0° C. for 10 min. A solution of the tosylate (200 mg, 0.56 mmol) from Step 1 in DMF (2 mL) was added to the reaction mixture dropwise over 5 min., and the reaction was heated at 95° C. for 10 h. The mixture was concentrated and water was added, and extracted with EtOAc. The organic layer was washed with saturated aq. NaHCO3 followed by water and brine. Organic layer was dried over anhy. Na2SO4 and the solvent was removed in vacuo to obtain the crude product, which was purified by silica gel flash chromatography to obtain the title product (150 mg, 73%) as a solid: MS; m/z 368 (M+H); 1H NMR (400 MHz, CDCl3); δ 1.46 (m, 9H), 1.84-2.03 (m, 4H), 3.39 (m, 2H), 3.73-3.93 (m, 3H), 4.10 (m, 2H), 6.84 (m, 2H), 7.08 (m, 2H), 7.17 (m, 2H), 7.26 (m, 3H): HPLC (UV), 99.8%.

Provenance & Evidence