2-Methylpiperidine → 5-Bromo-2-(2-methylpiperidin-1-YL)benzaldehyde

Participants

Reaction Conditions

Reaction Steps

2-Methylpiperidine (15.4 mL, 130.0 mmol) and anhydrous sodium carbonate (13.8 g, 130.0 mmol) were added into a solution of 5-bromo-2-fluorobenzaldehyde (13.2 g, 65.0 mmol) in DMSO (160 mL) and water (40 mL). The resulting mixture was heated at 120° C. for 16 hours. The reaction mixture was diluted with water (1 L) and extracted with Et2O (2×750 mL). The organic layers were washed with brine (500 mL, pH 5-6 adjusted with a 5N aqueous solution of HCl), combined and dried (MgSO4). The solvents were removed under reduced pressure to give the title compound as a brown yellow oil (16.3 g, 89%) used without further purification in the next step. HPLC (Method A), Rt 2.20 min (purity: 93.7%). HPLC/MS, M+(ESI): 282.1, 284.1. 1H NMR (CDCl3, 300 MHz) δ 10.40 (s, 1H), 7.93 (d, J=2.5 Hz, 1H), 7.62 (dd, J=8.6, 2.5 Hz, 1H), 7.12 (d, J=8.6 Hz, 1H), 3.17 (m, 1H), 3.06 (m, 1H), 2.81 (ddd, J=11.7, 7.6, 3.9 Hz, 1H), 1.89 (m, 1H), 1.83-1.65 (m, 3H), 1.58-1.42 (m, 2H), 0.91 (d, J=6.3 Hz, 3H).

Provenance & Evidence