Hydrochloric Acid → 4,5-Dichloro-2-nitrobenzoic acid

4,5-Dichloro-2-nitrobenzoic acid piperidine amide. A solution of 4,5-dichloro-2-nitrobenzoic acid methyl ester (0.29 g, 1.16 mmol) in 1:1 THF/methanol (4 mL) was stirred as 1 N aqueous LiOH (2 mL) was added. After 1 h, the mixture was acidified with 1 N HCl and extracted with EtOAc (3×). The combined organic layers were washed with brine, dried (MgSO4), filtered, and concentrated to provide crude 4,5-dichloro-2-nitrobenzoic acid as a light yellow solid (0.26 g, 0.90 mmol, 77%). The acid was refluxed in 4 mL thionyl chloride for 2 h, and the crude reaction mixture was concentrated in vacuo. Residual thionyl chloride was removed by the repeated addition and in vacuo stripping of DCM. The acid chloride was placed under high vacuum for 10 min, and then taken up in dry DCM (5 mL). The mixture was cooled in an ice bath. Piperidine (0.46 g, 5.4 mmol, 0.53 mL) was added, and the reaction mixture was allowed to stand at 0° C. overnight. The mixture was diluted with DCM, washed with 1 N HCl (2×), 5% aqueous NaHCO3 and brine, and dried (MgSO4). Filtration and concentration provided 0.32 g of the desired amide, which could not be separated from an impurity (10%) that corresponded to the product of displacement of a chlorine by an additional equivalent of piperidine. HPLC (reversed-phase): RT=9.35 min (90%), 10.58 (10%). MS (ESI): major m/z 303 [M+H]+, minor m/z 352 [M+H]+.

1. additionwas added
2. extractionextracted with EtOAc (3×)
3. washThe combined organic layers were washed with brine
4. dry with materialdried (MgSO4)
5. filtrationfiltered
6. concentrationconcentrated

ORD-Eintrag

ord-35c78cdfbec7410aa3bbd4775a1f23cf

Quelldatensatz

uspto-grants-2007_07

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07241759B2