Piconol → 3-Chloro-4-(2-pyridylmethoxy)aniline

Participants

Reaction Steps

To a mixture of 4-amino-2-chloro-phenol (1.0 g, 6.96 mmol), 2-hydroxymethylpyridine (1.52 g, 13.92 mmol), Ph3P (3.65 g, 13.92 mmol) in THF (30 ml) was added DIAD (2.74 ml, 13.92 mmol). The reaction mixture was stirred overnight and then concentrated in vacuo, and dissolved in EtOAc (100 ml). The resulting solution was extracted with 1N HCl (60 ml); the aqueous layer was washed with EtOAc (2×60 ml), then basified with solid NaHCO3. The mixture was extracted with EtOAc (2×100 ml) and the combined EtOAc extracts were washed with brine (1×40 ml), dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by silica gel flash column to give 1C (0.54 g, 33%) (50%–80% EtOAc-Hexanes). Analytical HPLC retention time=0.61 min. (YMC S5 ODS column 4.6×50 mm, 10–90% aqueous methanol over 4 minutes containing 0.2% phosphoric acid, 4 mL/min, monitoring at 220 nm) and a LC/MS M++1=235.

Provenance & Evidence