Lithium Hexamethyldisilazide → 4-(1-Cyclopropyl-4-methylpiperidin-4-yl)aniline

Participants

Reaction Conditions

Reaction Steps

To a suspended of 4-(4-bromophenyl)-1-cyclopropyl-4-methylpiperidine (341) (16.0 g, 54.5 mmol), (dicyclohexylphosphino)biphenyl (1.9 g, 5.4 mmol) and Pd2(dba)3 (2.5 g, 27.2 mmol) in anhydrous THF (100 mL) was added LiHMDS (1M, 109 mL, 109 mmol). The resulting mixture was purged with N2 and then stirred at 60° C. for overnight under N2 atmosphere. After cooled down to RT, the mixture was diluted with water (100 mL) and extracted with DCM (50 mL×3). The combined organic layers were washed with brine, dried, concentrated and subjected to silica flash column chromatography using 0 to 50% EtOAc in PE to give 4-(1-cyclopropyl-4-methylpiperidin-4-yl)aniline (342) (5 g, 40%) as a white solid. Proton NMR (CDCl3): δ 7.16 (2H, d, J=8.5 Hz), 6.69 (2H, d, J=8.6 Hz), 3.58 (2H, s), 2.82-2.65 (2H, m), 2.64-2.49 (2H, m), 2.14-2.04 (2H, m), 1.77-1.65 (2H, m), 1.21 (3H, s), 0.96-0.82 (1H, m), 0.56-0.28 (4H, m) ppm.

Provenance & Evidence