Acetic Acid → HCID 86749504, compound

Participants

Reaction Conditions

Reaction Steps

A finely divided mixture of 4-hydroxy-3-methoxyphenethylamine (9.9 g) and 1-phenylcyclopentane carboxylic acid (11.9 g) was heated at 200° C. under nitrogen for two hours. The melt was cooled slightly and added to a 1:1 mixture of glacial acetic acid and water. A solid crystallised which was removed by filtration and washed with acetic acid. The filtrate was basified with excess sodium carbonate and extracted with ether. The extract was washed with 4N hydrochloric acid. The ether extract yielded a residue which was heated under reflux in a nitrogen atmosphere with acetonitrile (156 ml) and phosphorus oxychloride (18.7 ml) for one hour. The solvent was removed and water was added to the residue. The mixture was warmed and ethanol was added. The resulting solution was heated at 90°-95° C. for one hour and cooled. Ethanol was added to dissolve any solid and the solution basified with aqueous ammonia solution. Sodium borohydride (2.5 g in total) was added portionwise and the solvents removed by evaporation. The residue was partitioned between water and ethyl acetate to give a solid which was collected by filtration, washed with water and dried in air. The solid was dissolved in a mixture of 37-40% aqueous formaldehyde solution (27 ml) and formic acid (15 ml) and the solution warmed to 60° C. for two hours. Ice was added and the mixture basified with aqueous ammonia solution. The resulting mixture was extracted with ether. The extract was dried and the solvent removed to give a residue which was dissolved in ether. The extract was filtered, dried and ethereal oxalic acid was added. A solid was deposited. The ether was removed by decantation and ethyl acetate was added and the mixture heated at reflux. The solid product was triturated under the ethyl acetate, collected by filtration washed with ethyl acetate and dried in air to give 7-hydroxy-6-methoxy-2-methyl-1-(1-phenylcyclopentyl-1,2,3,4-tetrahydroisoquinoline oxalate, m.p. 172° C. (dec).

Provenance & Evidence