Water → Ammonia

Participants

Reaction Conditions

Reaction Steps

4′-Chloro-3-hydroxy-2-nitrobenzanilide (1.43 g) was suspended in 50 ml of methanol, then 5 ml of distilled water, 2.80 g of reduced iron and 530 mg of ammonium chloride were added thereto and the mixture was stirred at 60° C. for 2 hours. The reaction was filtered through Celite and concentrated in vacuo. To the resulting residue was added a saturated saline solution and the mixture was extracted with chloroform. The organic layer was dried over magnesium sulfate and concentrated in vacuo. The resulting residue and 320 mg of 1-isopropylpyridine-4-carbaldehyde were suspended in 14 ml of toluene, then 37 mg of p-toluene sulfonic acid hydrate were added thereto and the mixture was heated to reflux for 24 hours together with removal of water by an azeotropic operation. This was concentrated in vacuo, to the resulting residue were added 14 ml of acetic acid and 350 mg of a boran-trimethylamine complex and the mixture was stirred at 70° C. for 17 hours. This was concentrated in vacuo, a 5% aqueous solution of sodium bicarbonate was added to the resulting residue and the mixture was extracted with chloroform. The organic layer was dried over magnesium sulfate and concentrated in vacuo. The resulting residue was purified by means of a silica gel column chromatography using chloroform:methanol:saturated aqueous ammonia (100:10:1) as an eluate to give 380 mg of crudely purified 4′-chloro-3-hydroxy-2-{[(1-isopropyl-4-piperidyl)methyl]amino}benzanilide. The crudely purified product (380 mg) was purified by means of an ODS column chromatography using 0.001N hydrochloric acid:methanol (10:3) as an eluate and then freeze-dried to give 162 mg of 4′-chloro-3-hydroxy-2-{[(1-isopropyl-4-piperidyl)methyl]amino}benzanilide hydrochloride.

Provenance & Evidence