Trifluoroacetic acid → 4-[4-(2-Pyrrolidin-1-yl-ethoxy)-benzyl]-phenol

Participants

Reaction Steps

To a stirred solution of 1-[2-(4-bromo-phenoxy)-ethyl]-pyrrolidine (2.89 g, 10.7 mmol) in THF (30 mL) was added dropwise 1.6 M solution in hexanes n-BuLi (7 mL, 10.2 mmol) over a 5-min period at −78° C. The mixture was stirred at −78° C. for 15 min before 4-trimethylsilyloxybenzaldehyde (2.08 g, 10.7 mmol) was added. The mixture was allowed to warm to rt during 20 min and quenched with water. Extraction with CH2Cl2, drying (MgSO4), filtration and evaporation provided the crude diarylmethanol which was dissolved in CH2Cl2 (30 mL) and stirred with triethylsilane (4 mL) and TFA (5 mL) for 16 h at rt. Evaporation gave 3.0 g (84%) 4-[4-(2-pyrrolidin-1-yl-ethoxy)-benzyl]-phenol. This was carbamoylated using general procedure 1 (CH2Cl2 was used as solvent) to give the title product after purification by preparative HPLC (Gilson) (35%, oil).

Provenance & Evidence