8-Hydroxy-5-(1-hydroxy-2-((1-methylethyl)amino)butyl)-2(1H)-quinolinone → 5-(1-Hydroxy-2-isopropylaminobutyl)-8-isobutyryloxycarbostyril hydrochloride

Participants

Reaction Steps

3 g of 5-(1-hydroxy-2-isopropylaminobutyl)-8-hydroxycarbostyril was added to 200 ml of anhydrous chloroform, and 3 ml of isobutyric anhydride was added dropwise to the mixture. The resulting mixture was stirred for 5 hours at room temperature, and the solvent was removed by distillation under reduced pressure. Petroleum ether was added to the residue, and the crystals formed were separated by filtration. The crystals were rendered neutral with 50 ml of a cold saturated aqueous solution of sodium bicarbonate, and insoluble material was separated by filtration and washed with water. The resulting material which was found to be a mixture of about 7 components by thin layer chromatography was then subjected to silica gel column chromatography using a silica gel of Grade C-200 (trade name of Wako Junyaku, Japan) and a mixture of chloroform and methanol (20:1 by volume) as an eluant to obtain an eluate containing four main components. The solvent was then removed by distillation from the eluate, and 5 ml of a saturated ethanolic solution of hydrogen chloride was added to the residue. Petroleum ether was added to the mixture, and the precipitated crystals were separated by filtration and recrystallized from acetone to obtain, as main components, 1.5 g of 5-(1-isobutyryloxy-2-isopropylaminobutyl)-8-isobutyryloxycarbostyril hydrochloride monohydrate having a melting point of 198°-199° C., 0.1 g of 2,8-diisobutyryloxy-5-(1-hydroxy-2-isopropylaminobutyl)quinoline hydrochloride having a melting point of 201°-203° C. (with decomposition), 0.4 g of 5-(1-hydroxy-2 -isopropylaminobutyl)-8-isobutyryloxycarbostyril hydrochloride having a melting point of 228°-229° C. (with coloration and decomposition), and 0.1 g of 2-isobutyryloxy-5-(1-hydroxy-2-isopropylaminobutyl)-8-hydroxyquinoline hydrochloride having a melting point of 225°-226.5° C. (with coloration and decomposition).

Provenance & Evidence