2-Piperidone → 1-(4-Amino-3-fluoro-phenyl)-piperidin-2-one

Participants

Reaction Steps

2-Fluoro-4-iodoaniline (10.0 g, 42.2 mmol) was combined with δ-valerolactam (6.27 g, 63.3 mmol), CuI (0.804 g, 4.22 mmol), and K3PO4 (22.4 g, 105 mmol). 1,4-Dioxane (60 mL) was added followed by trans-1,2-diaminocyclohexane (1.01 mL, 8.44 mmol). The mixture was heated to reflux for 22 h before cooling and diluting with EtOAc. The mixture was filtered through a plug of silica, eluting with EtOAc, and the filtrate concentrated under reduced pressure. Purification of the crude product by flash chromatography revealed 7 (3.40 g, 39%) as a brown solid. MS: APCI (AP+): 209.1 (M)+.

Provenance & Evidence