Thionyl Chloride → 4-Bromo-2-nitrobenzoyl chloride

4-Bromo-2-nitrobenzoic acid piperidine amide. A suspension of 4-bromo-2-nitrobenzoic acid (0.60 g, 2.44 mmol) in thionyl chloride (8 mL) was heated to reflux for 2 h. The reaction mixture became homogeneous. The mixture was cooled and concentrated in vacuo to give 4-bromo-2-nitrobenzoyl chloride as a white solid, which was used immediately in the following reaction. 1H NMR (400 MHz, CDCl3): 8.20 (d, J=1.9 Hz, 1H), 7.92 (dd, J=8.2, 1.9 Hz, 1H), 7.65 (d, J=8.2 Hz, 1H). To a solution of 4-bromo-2-nitrobenzoyl chloride (2.44 mmol) in DCM (15 mL) at ambient temperature was added piperidine (1.2 mL, 12.2 mmol). The reaction mixture was stirred for 3 h then poured into water and extracted with DCM (2×). The combined organic extracts were washed with brine, dried (MgSO4), and concentrated in vacuo. The residue was purified by flash chromatography (hexanes/EtOAc) to afford the title amide as a white solid (0.52 g, 76%). MS (ESI): m/z 313 [M+H]+. 1H NMR (400 MHz, CDCl3): (rotameric broadening) 8.33 (d, J=1.9 Hz, 1H), 7.82 (dd, J=8.1, 1.9 Hz, 1H), 7.27 (d, J=8.1 Hz, 1H), 3.82–3.65 (bm, 2H), 3.16 (t, J=5.6 Hz, 2H), 1.90–1.35 (bm, 6H).

1. temperaturewas heated
2. temperatureto reflux for 2 h
3. temperatureThe mixture was cooled
4. concentrationconcentrated in vacuo

ORD-Eintrag

ord-b759de4584c249cf980427d6aa8be9b1

Quelldatensatz

uspto-grants-2007_07

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07241759B2