4-Hydroxybenzoic Acid → HCID 9842208, compound

Participants

Reaction Steps

To a mixture of 4-hydroxybenzoic acid (2.5 g, 0.0182 mol), 1-hydroxybenzotriazole hydrate (3.33 g, 0.0218 mol), benzyl 4-(aminomethyl)piperidine-1-carboxylate (4.5 g, 0.0182 mol) and triethylamine (3.03 mL, 0.0218 mol) in DMF (30mL) was added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (4.2 g, 0.0218 mol) and the mixture allowed to stir at rt for 18 h. The mixture was quenched into water (200 mL) and extracted with ethyl acetate (200 nL). The ethyl acetate extract was washed with 10% aqueous sodium bicarbonate (100 mL), brine (50 mL), dried over sodium sulfate, and filtered. The filtrate was concentrated in vacuo and the residue chromatographed on silica using 10–20% acetone/dichloromethane to give 6.3 g of 4-[(4-hydroxy-benzoylamino)-methyl]-piperidine-1-carboxylic acid benzyl ester as a foam. The foam was dissolved in hot isopropyl acetate (125 mL), filtered, and allowed to cool and crystallize. The reaction volume was reduced in vacuo to 50 mL, allowed to stir overnight at rt and filtered. The resulting solid was dried in vacuo (50° C.) yielding the 4-[(4-hydroxy-benzoylamino)-methyl]-piperidine-1-carboxylic acid benzyl ester.

Provenance & Evidence