Lithium Hexamethyldisilazide → Tert-butyl 4-(4-aminophenyl)-4-methylpiperidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

A sealed tube was charged with tert-butyl 4-(4-bromophenyl)-4-methylpiperidine-1-carboxylate (286) (2.6 g, 7.37 mmol), (dicyclohexylphosphino)biphenyl (65 mg, 0.18 mmol), Pd2(dba)3 (68 mg, 0.074 mmol) and LiHMDS (1M, 14.7 mL, 14.7 mmol) in anhydrous THF (15 mL). The resulting mixture was purged with N2 stream and stirred in 65° C. bath for overnight. After being cooled to RT, the mixture was diluted with water (10 mL) and extracted with DCM (5 mL×3). The combined organic layers were washed with brine, dried, concentrated in vacuo, and subjected to silica flash column chromatography using 0 to 30% EtOAc in PE to afford tert-butyl 4-(4-aminophenyl)-4-methylpiperidine-1-carboxylate (287) (750 mg, 36%) as a white solid. Proton NMR (CDCl3): δ 7.13 (2H, d, J=8.5 Hz), 6.69 (2H, d, J=8.5 Hz), 3.67-3.57 (2H, m), 3.54-3.44 (2H, m), 3.43-3.33 (2H, m), 2.03 (2H, s), 1.67-1.61 (2H, m), 1.47 (9H, s), 1.22 (3H, s) ppm.

Provenance & Evidence