Diisopropylethylamine → HCID 86695326, compound

Participants

Reaction Steps

To a solution of 4-[(3-bromophenyl)carboxymethoxy]piperidine-1-carboxylic acid tert-butyl ester (general procedure 165D+saponification)(1 g) in acetonitrile (10 mL) are added 3,4,5-trifluorobenzene-1,2-diamine (470 mg), 2-chloro-1-methylpyridinium iodide (802 mg) and dropwise diisopropylethylamine (1.1 mL). The reaction mixture is stirred at room temperature for 2 hours. Solvent is removed under reduced pressure and the residue diluted with ethyl acetate. The organic phase is washed with water, dried over magnesium sulfate and concentrated under reduced pressure. The residue is purified by chromatography over silica gel (gradient dichloromethane/methanol/ammonia from 98/2/0.2 to 90/10/1) to get 4-[(6-amino-2,3,4-trifluorophenylcarbamoyl)(3-bromophenyl)methoxy]piperidine-1-carboxylic acid tert-butyl ester. This intermediate is dissolved in acetic acid (15 mL) and the reaction mixture is refluxed for 3 hours. Acetic acid is removed under reduced pressure. Water is added to the residue and the solution is basified by adding a solution of saturated sodium hydrogencarbonate to pH 10. The aqueous phase is extracted with ethyl acetate. The pooled organic extracts are dried over magnesium sulfate and concentrated under reduced pressure. The residue is purified by chromatography over silica gel (gradient dichloromethane/methanol/ammonia from 98/2/0.2 to 90/10/1) to yield 2-[(3-bromophenyl)(piperidin-4-yloxy)methyl]-5,6,7-trifluoro-1H-benzimidazole.

Provenance & Evidence